Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells (RGCs) in a rat chronic ocular hypertension (COH) model. Here, we investigated the expression of endothelin...Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells (RGCs) in a rat chronic ocular hypertension (COH) model. Here, we investigated the expression of endothelin-1 (ET-1), a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure (IOP) was induced in the right eye of SD rats using argon laser photocoagulation. (1) The expression of ET-1, ETA and ETB in normal and COH retinas was studied. (2) Some COH rats were fed daily with Lycium barbarum Polysaccharides (LBP) using 1 mg/kg or phosphate-buffered saline (PBS) for 3 weeks (started 1 week before photocoagulation). The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that (1) Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. (2) After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. (3) By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.展开更多
To investigate the effects of L-tetrahydropalmatine (L-THP) on ener-gy metabolism, endothelin-1 (ET-1 ) and NO during acute cerebral ischemia-reperfusion of rats, 24 Wistar rats were randomly divided into four groups,...To investigate the effects of L-tetrahydropalmatine (L-THP) on ener-gy metabolism, endothelin-1 (ET-1 ) and NO during acute cerebral ischemia-reperfusion of rats, 24 Wistar rats were randomly divided into four groups, with 6rats in each group: sham-operation group, simple ischemia group, ischemia-reperfusion group and treatment group (L-THP group). Cerebral ATP, lactate,ET-1 and NO levels were measured in all groups. Our results showed that treat-ment with L-THP could increase cerebral ATP levels, but decrease cerebral lac-tate, ET-1 and NO concentrations during ischemia-reperfusion in the treatmentgroup. It is concluded that L-THP could improve cerebral energy metabolism and protect the injured brain tissue, the mechanism of which might be related to suppression of overproduction of ET-1 and NO.展开更多
AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surger...AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surgery to induce portal hypertension or sham surgery.Development of portal hypertension was determined by measuring the splenic pulp pressure,abdominal aortic flow and portal systemic shunting.To measure splenic pulp pressure,a microtip pressure transducer was inserted into the spleen pulp.Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery.Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds.Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration.In addition,thoracic aorta endothelin-1contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph.RESULTS:In wild type and i NOS-/-mice splenic pulp pressure increased from 7.5±1.1 mm Hg and 7.2±1 mm Hg to 25.4±3.1 mm Hg and 22±4 mm Hg respectively.In e NOS-/-mice splenic pulp pressure was increased after 1 d(P=NS),after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls(6.9±0.6 mm Hg and 7.3±0.8 mm Hg respectively,P=0.3).Abdominal aortic flow was increased by 80%and 73%in 7 d portal vein ligated wild type and i NOS when compared to shams,whereas there was no significant difference in 7 d portal vein ligated e NOS-/-mice when compared to shams.Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type,e NOS-/-and i NOS-/-sham mice(50%±8%,73%±9%and 47%±9%respectively).Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group.Abdominal aortic flow was reduced by 19%±9%,32%±10%and 9%±9%in wild type,e NOS-/-and i NOS-/-mice respectively.CONCLUSION:Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent.Moreover,portal hypertension in the portal vein ligation model is independent of ET-1 function.展开更多
Endothelin-1(ET-1), a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine(TAU), a naturally occurring free amino acid, is known for its neuropro...Endothelin-1(ET-1), a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine(TAU), a naturally occurring free amino acid, is known for its neuroprotective and antioxidant properties. Hence, we evaluated its neuroprotective properties against ET-1 induced retinal and optic nerve damage. ET-1 was administered intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co-or post-treatment. Animals were euthanized seven days post TAU injection. Retinae and optic nerve were examined for morphology, and were also processed for caspase-3 immunostaining. Retinal redox status was estimated by measuring retinal superoxide dismutase, catalase, glutathione, and malondialdehyde levels using enzyme-linked immuosorbent assay. Histopathological examination showed significantly improved retinal and optic nerve morphology in TAU-treated groups. Morphometric examination showed that TAU pre-treatment provided marked protection against ET-1 induced damage to retina and optic nerve. In accordance with the morphological observations, immunostaining for caspase showed a significantly lesser number of apoptotic retinal cells in the TAU pre-treatment group. The retinal oxidative stress was reduced in all TAU-treated groups, and particularly in the pre-treatment group. The findings suggest that treatment with TAU, particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1 and hence prevents the changes in the morphology of retina and optic nerve. The protective effect of TAU against ET-1 induced retinal and optic nerve damage is associated with reduced retinal oxidative stress.展开更多
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is st...Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 (ET-1) into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.展开更多
The effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin on the enhanced hypoxia induced factor-let (HIF-lct) and endothelin-1 (ET-1) expression, elevated systolic blood pres...The effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin on the enhanced hypoxia induced factor-let (HIF-lct) and endothelin-1 (ET-1) expression, elevated systolic blood pressure under chronic intermittent hypoxia (CIH) condition and its action mechanism were investigated. Thirty healthy 8-week old Sprague-Dawley (SD) male rats were randomly divided into three groups (n=10 each): sham group, CIH group, and apocynin-treated CIH group. Tail artery systolic blood pressure was measured by tail-cuff method. Real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression of HIF-lu and ET-1 in the carotid body, and the HIF-1a protein expression was examined by using Western blotting. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using colorimetric method. In addition, the plasma ET-1 and HIF-1a levels were measured by using enzyme-linked immunosorbent assay. It was found that CIH exposure was associated with increased MDA levels, and apo- cynin-treated CIH animals showed reduction in MDA levels. Apocynin treatment prevented CIH-induced hypertension as well as CIH-induced decrease in SOD. The increases of HIF-1a and ET-1 mRNA along with HIF-la protein expression in the carotid body, and elevated circulating HIF-1a and ET-1 levels were observed in CIH-exposed animals. Treatment with apocynin significantly decreased the ET-1 mRNA, HIF-lct protein expression and circulating HIF-la level in CIH-exposed animals, and there was no statistically significant difference in the HIF-lu mRNA expression between CIH group and apo- cynin-treated group. These results indicated that apocynin alleviated CIH-induced hypertension by inhibiting NADPH oxidase, further leading to the reduced vasoconstrictor ET-1 level and oxidative stress. HIF-1a/ET-1 system signal pathway may interact with CIH-induced NADPH oxidase-dependent oxidative stress. Inhibition of NADPH oxidase activity may hopefully serve as a useful strategy for prevention and treatment of obstructive sleep apnea hypopnea syndrome-induced hypertension.展开更多
Objective: To compare the levels of p38 mitogen-activated protein kinase (MAPK), soluble endoglin and endothelin-1 in the serum of patients with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet...Objective: To compare the levels of p38 mitogen-activated protein kinase (MAPK), soluble endoglin and endothelin-1 in the serum of patients with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and normal pregnancies. Methods: This study was an observational analytic cross-sectional study performed at Wahidin Sudirohusodo Hospital, Makassar, Indonesia, in the period of 5th February 2016 to 20th January 2017. P38 MAPK, soluble endoglin and endothelin-1 levels of patients with normal pregnancies, severe preeclampsia and HELLP syndrome were measured by enzyme-linked immunoabsorbentassay technique, using kits of human soluble endoglin, endothelin-1 and p38 MAPK, Quantikine immunoassay: R&D System Inc. Results: Level of serum p38 MAPK in HELLP syndrome group was higher than in severe preeclampsia and normal pregnancy groups. Soluble endoglin and endothelin-1 levels in pregnancies with severe preeclampsia and HELLP syndrome were higher than normal pregnancy but there was no significant difference between these two groups (P>0.05). Levels of p38 MAPK, soluble endoglin and endothelin-1 also had a positive linear correlation with systolic and diastolic blood pressures (P<0.05). Conclusions: P38 MAPK in serum may be a marker for evidence of the severe hypoxia and its application may be considered for the diagnosis of HELLP syndrome.展开更多
AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.MET...AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.METHODS: The experimental study was performed on20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate(DOCA)10 mg/kg twice a week and administered 0.9% Na Cl solution daily for 2, 6, and 10 wk. Blood pressure(BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, e NOS, ET-1 receptor A(ETRA), ET-1receptor B(ETRB), and phosphorylated myosin light chain kinase(MLCK), and caldesmon(Ca D) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS: BP significantly increased in all of the hypertension groups compared to control(P =0.001).Peak IOP elevation(7.78±4.14 mm Hg) and RGC apoptosis(576.15±33.28 Au) occurred on 2wk of hypertension. ET-1expression(1238.6±55.1 Au) and e NOS expression(2814.2±70.7 Au) were found highest in 2wk of hypertension,although the ratio of ET-1/e NOS decreased since 2wk.ETRAreached peak expression in 10 wk of hypertension(1219.4 ±6.3 Au), while ETRBsignificantly increased only in 2 weeks group(1069.2 ±9.6 Au). The highest MLCK expression(1190.09±58.32 Au), Ca D(1670.28±18.36 Au)were also found in 2wk of hypertension.CONCLUSION: Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension.展开更多
Objective To investigate whether plasma big endothelin-1(ET-1) predicts ventricular arrythmias(VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator(ICD) indication patigents. Methods ...Objective To investigate whether plasma big endothelin-1(ET-1) predicts ventricular arrythmias(VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator(ICD) indication patigents. Methods In total, 207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analyzed. The cohort was divided into three groups according to baseline plasma big ET-1 tertiles: tertile 1(< 0.38 pmol/L, n = 68), tertile 2(0.38–0.7 pmol/L, n = 69), and tertile 3(> 0.7 pmol/L, n = 70). The primary endpoints were VAs. The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation. Results During a mean follow-up period of 25.6 ± 13.9 months, 38(18.4%) VAs and 78(37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class(r = 0.165, P = 0.018), serum creatinine concentration(Scr;r = 0.147, P = 0.034), high-sensitivity C-reactive protein(hs-CRP;r = 0.217, P = 0.002), Lg NT-pro BNP(r = 0.463, P < 0.001), left ventricular end diastolic diameter(LVEDD;r = 0.234, P = 0.039) and negatively correlated with left ventricular ejection fraction(LVEF;r =-0.181, P = 0.032). Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events(P < 0.05). In multivariate Cox regression models, big ET-1 was an independent risk factor for VAs(hazard ratio(HR) = 3.477, 95% confidence interval(CI): 1.352–8.940, P = 0.010, tertile 2 vs. tertile 1;HR = 4.112, 95% CI: 1.604–10.540, P = 0.003, tertile 3 vs. tertile 1) and end-stage events(HR = 2.804, 95% CI: 1.354–5.806, P = 0.005, tertile 2 vs. tertile 1;HR = 4.652, 95% CI: 2.288–9.459, P < 0.001, tertile 3 vs. tertile 1). Conclusions In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.展开更多
The present study investigated a possible mechanism for endogenous endothelin-1 (ET-1) regulation of atrial natriuretic peptide (ANP) secretion in isolated perfused acute hypoxic rabbit atria. Acute hypoxia significan...The present study investigated a possible mechanism for endogenous endothelin-1 (ET-1) regulation of atrial natriuretic peptide (ANP) secretion in isolated perfused acute hypoxic rabbit atria. Acute hypoxia significantly enhanced the release of ET-1 and the expression of the ET receptor (ETR) type A and B (ETR<sub>A</sub> and ETR<sub>B</sub>) in atrial tissues, with a concomitant increase in ANP secretion. The ETR<sub>A</sub> or ETR<sub>B</sub> antagonist, BQ123 (0.3 μmol/L) or BQ788 (0.3 μmol/L), respectively attenuated hypoxia-induced ANP secretion. Both antagonists significantly attenuated the levels of hypoxiainduced atrial phosphorylated (p)-extracellular signal-regulated kinase (ERK) and p-protein kinase B (Akt). The ERK and Akt inhibitors, PD098059 (30 μmol/L) and LY294002 (30 μmol/L), respectively mimicked the effect of the ETR antagonists. These results demonstrated that acute hypoxia- mediated atrial ET-1 regulated ANP secretion through ETR and the subsequent mitogenactivated protein kinase (MAPK)/ERK and ETR-phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. These pathways may mediate atrial endocrine functions under hypoxic conditions.展开更多
Objective:To explore the protective effect of acupuncture against myocardial injury in rats with stress-induced prehypertension (SIPH) by observing the genetic expression of myocardial endothelin-1 (ET-1) and atrial n...Objective:To explore the protective effect of acupuncture against myocardial injury in rats with stress-induced prehypertension (SIPH) by observing the genetic expression of myocardial endothelin-1 (ET-1) and atrial natriuretic peptide (ANP).Methods:Thirty-six Wistar rats were randomized into three groups:the control group,model group,and model + acupuncture (AP) group (n =12 rats per group).During the 11-day modeling period,the model group and the model + AP group experienced plantar electric stimulation in combination with noise exposure,and daily acupuncture intervention was applied simultaneously in the model + AP group;the control group did not experience modeling or acupuncture.Systolic pressure (SP) was measured the day before modeling began,and on the 3rd,5th,7th,9th,and 11th day after modeling initiation.On the 12th day,histopathological observation of the left ventricle was made with hematoxylin-eosin staining and quantitative genetic expression of myocardial ET-1,and ANP was tested by quantitative real-time polymerase chain reaction (PCR).Results:SP was higher in the model group than the control group on the 3rd,5th,7th,9th,and 11th days (all P <.01).SP in the model + AP group was lower than that in the control group on the 5th and 7th days (respectively,P =.008,P =.002) and on the 9th and 11th days (P =.029,P =.039).Hematoxylin-eosin staining showed normal myocardial cellular structure in the control group.The model group showed disordered arrangement of cardiac cells with morphological changes in some nuclei,including enlargement or dissolution;there was also infiltration of inflammatory cells and proliferation of collagen fibers.In the model + AP group,most of the myocardial cells were normally structured,and only part of the cells had morphological changes with enlarged nuclei or dissolution.Real-time PCR showed that expression of ET-1 and ANP mRNA in the model group was greater than the control group (respectively,P =.024,P =.000101).The model + AP group had lower expression of ET-1 and ANP mRNA compared with the model group (respectively,P =.033,P =.043).Conclusion:Acupuncture may lower blood pressure and downregulate the genetic expression of myocardial ET-1 and ANP in SIPH rats,suggesting a protective effect of acupuncture against myocardial damage.展开更多
BACKGROUND: Several studies have confirmed that endothelin and endorphin are involved in the occurrence of cerebral vasospasm. However, the correlation of these factors to acute cerebral infarction-related risk facto...BACKGROUND: Several studies have confirmed that endothelin and endorphin are involved in the occurrence of cerebral vasospasm. However, the correlation of these factors to acute cerebral infarction-related risk factors needs to be confirmed. OBJECTIVE: To detect endothelin-1 (ET-1) and beta-endorphin (β -EP) levels in plasma of patients with acute cerebral infarction, and to analyze the correlations of these factors to smoking, alcohol abuse, hypertension, diabetes mellitus, diseased region, diseased degree, gender, and other factors related to acute cerebral infarction. DESIGN: A case-control observation. SETTING: First Department of Neurology, Guangdong Hospital of Traditional Chinese Medicine; Department of Neurology, Second Affiliated Hospital of Sun Yat-sen University. PARTICIPANTS: Sixty-nine inpatients with acute cerebral infarction were admitted to the Department of Neurology, Second Affiliated Hospital of Sun Yat-sen University (March 2003-January 2004) and First Department of Neurology, Guangdong Hospital of Traditional Chinese Medicine (March July 2004) and recruited for this study. All 69 inpatients corresponded to the diagnosis criteria of acute cerebral infarction, formulated in the National Working Conference of Cerebrovascular Disease in 1998, and were confirmed as acute cerebral infarction by CT/MRI. The patient group consisted of 35 males [(644- 12) years old] and 34 females[ (674- 13 ) years old]. Among them, 9 patients were smokers, 7 were alcohol users, 48 had a history of hypertension, and 16 had a history of diabetes mellitus. CT/MRI examinations revealed that 35 patients presented with left focus sites, 11 with right ones and 23 with bilateral ones. Following attack, 24 patients had Barthel Index Scale grading 〈 40 points, 21 patients 40-50 points, and 24 patients 〉 60 points. An additional 59 healthy individuals, who received health examinations simultaneously, were included as controls. Among the control subjects, there were 37 males [(62±10) years old] and 22 females [(65±11) years old]. Among them, 7 patients were smokers, and 6 were alcohol users. All controls had no history of stroke, hypertension, or diabetes mellitus. Informed consents of laboratory measurements were obtained from all subjects, and this study was approved by the Hospital Ethics Committee. METHODS: ① Following admission, all subjects were scored by Barthel Index Scale (BIS) and Hamilton Depression Scale. Meanwhile, hypertension, diabetes mellitus, gender, smoking, drinking, and other conditions were recorded. CT/MRI examination was conducted to identify the focus site.②On the 2^nd day after admission, ET-1 and β -EP plasma levels were measured with an automatic ET-1 and β -EP analysis kit. MAIN OUTCOME MEASURES: ET-1 and β -EP plasma levels and their correlation to acute cerebral infarction-related factors. RESULTS: Sixty-nine patients with acute cerebral infarction, and an additional 59 healthy individuals participated in the final analysis. β ET-1 [(63.80±27.65) ng/L vs. (46.50±9.36) ng/L, P 〈 0.05] and β - EP [(94.18±33.94) mg/L vs. (51.87±23.43) mg/L, P 〈 0.05] levels of the patient group were obviously higher than respective values of the control group. ② The ET-1 and β -EP levels of patients with cerebral infarction did not correlate to hypertension, diabetes mellitus, BIS, depression, cerebral infarct focus, disease course, gender, smoking or drinking (P 〉 0.05). CONCLUSION: The ET-I and β-EP levels of patients with acute cerebral infarction increased, but they were not obviously associated with disease course, blood pressure, blood glucose, BIS, or other common cerebral infarction-related factors.展开更多
BACKGROUND Previous evidence has implied that obesity is an independent risk factor for developing cancer.Being closely related to obesity,type 2 diabetes mellitus provides a suitable environment for the formation and...BACKGROUND Previous evidence has implied that obesity is an independent risk factor for developing cancer.Being closely related to obesity,type 2 diabetes mellitus provides a suitable environment for the formation and metastasis of tumors through multiple pathways.Although bariatric surgeries are effective in preventing and lowering the risk of various types of cancer,the underlying mechanisms of this effect are not clearly elucidated.AIM To uncover the role and effect of sleeve gastrectomy(SG)in preventing lung cancer in obese and diabetic rats.METHODS SG was performed on obese and diabetic Wistar rats,and the postoperative transcriptional and translational alterations of the endothelin-1(ET-1)axis in the lungs were compared to sham-operated obese and diabetic rats and age-matched healthy controls to assess the improvements in endothelial function and risk of developing lung cancer at the postoperative 4 th,8 th,and 12 th weeks.The risk wasalso evaluated using nuclear phosphorylation of H2 A histone family member X as a marker of DNA damage(double-strand break).RESULTS Compared to obese and diabetic sham-operated rats,SG brought a significant reduction to body weight,food intake,and fasting blood glucose while improving oral glucose tolerance and insulin sensitivity.In addition,ameliorated levels of gene and protein expression in the ET-1 axis as well as reduced DNA damage indicated improved endothelial function and a lower risk of developing lung cancer after the surgery.CONCLUSION Apart from eliminating metabolic disorders,SG improves endothelial function and plays a protective role in preventing lung cancer via normalized ET-1 axis and reduced DNA damage.展开更多
To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia1...To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia11y reported by various authors. We have performed investigations in anesthetized Sprague-Dawley rats- Intracisternal injection (i. c. ) of ET-l (10-11, 10-10, 10-9 mol/kg) could induce acute dose-dependent CVS, furthermore, the highest dose of ET-l (lO-’ mo1/kg) had a biphasic response in CVS of a 24-hour duration. However, the CVS by ET-1 (10-9 mol/kg) could be prevented effectively by previous i. c. of BQ-123 in a dose-dependent manner (10-9, 10-8, 10-7 mol/kg), of which the i. c- of BQ-123 (10-7mol/kg) could abolish the CVS completely. i. c. of BQ-123 (10-7 mol/kg) before SAH induced by a single i. c, of 150 pl autologous fresh blood directly to the Willis circle cou1d prevent the following CVS largely, which was a biphasic response and long-lasting (duration of 72 h). We conclude that subarachnoid application of ETA-receptor antagonist can effecti vely prevent CVS induced by ET-1 and SAH, and ET-1 may be the major mediator responsible for the CVS following SAH.展开更多
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
基金supported by the Azalea (1972) Education fund to KFSo and RCCCFundamental Research Fund for The Centre Universities,No.21609101
文摘Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells (RGCs) in a rat chronic ocular hypertension (COH) model. Here, we investigated the expression of endothelin-1 (ET-1), a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure (IOP) was induced in the right eye of SD rats using argon laser photocoagulation. (1) The expression of ET-1, ETA and ETB in normal and COH retinas was studied. (2) Some COH rats were fed daily with Lycium barbarum Polysaccharides (LBP) using 1 mg/kg or phosphate-buffered saline (PBS) for 3 weeks (started 1 week before photocoagulation). The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that (1) Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. (2) After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. (3) By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.
文摘To investigate the effects of L-tetrahydropalmatine (L-THP) on ener-gy metabolism, endothelin-1 (ET-1 ) and NO during acute cerebral ischemia-reperfusion of rats, 24 Wistar rats were randomly divided into four groups, with 6rats in each group: sham-operation group, simple ischemia group, ischemia-reperfusion group and treatment group (L-THP group). Cerebral ATP, lactate,ET-1 and NO levels were measured in all groups. Our results showed that treat-ment with L-THP could increase cerebral ATP levels, but decrease cerebral lac-tate, ET-1 and NO concentrations during ischemia-reperfusion in the treatmentgroup. It is concluded that L-THP could improve cerebral energy metabolism and protect the injured brain tissue, the mechanism of which might be related to suppression of overproduction of ET-1 and NO.
基金Supported by Indiana University department of surgery and Lilly INGEN research fund provided support for the Research performed in this manuscript
文摘AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surgery to induce portal hypertension or sham surgery.Development of portal hypertension was determined by measuring the splenic pulp pressure,abdominal aortic flow and portal systemic shunting.To measure splenic pulp pressure,a microtip pressure transducer was inserted into the spleen pulp.Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery.Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds.Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration.In addition,thoracic aorta endothelin-1contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph.RESULTS:In wild type and i NOS-/-mice splenic pulp pressure increased from 7.5±1.1 mm Hg and 7.2±1 mm Hg to 25.4±3.1 mm Hg and 22±4 mm Hg respectively.In e NOS-/-mice splenic pulp pressure was increased after 1 d(P=NS),after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls(6.9±0.6 mm Hg and 7.3±0.8 mm Hg respectively,P=0.3).Abdominal aortic flow was increased by 80%and 73%in 7 d portal vein ligated wild type and i NOS when compared to shams,whereas there was no significant difference in 7 d portal vein ligated e NOS-/-mice when compared to shams.Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type,e NOS-/-and i NOS-/-sham mice(50%±8%,73%±9%and 47%±9%respectively).Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group.Abdominal aortic flow was reduced by 19%±9%,32%±10%and 9%±9%in wild type,e NOS-/-and i NOS-/-mice respectively.CONCLUSION:Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent.Moreover,portal hypertension in the portal vein ligation model is independent of ET-1 function.
基金the financial support by Universiti Teknologi MARA under grant No.600-IRMI/DANA5/3/BESTARI(006/2017)
文摘Endothelin-1(ET-1), a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine(TAU), a naturally occurring free amino acid, is known for its neuroprotective and antioxidant properties. Hence, we evaluated its neuroprotective properties against ET-1 induced retinal and optic nerve damage. ET-1 was administered intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co-or post-treatment. Animals were euthanized seven days post TAU injection. Retinae and optic nerve were examined for morphology, and were also processed for caspase-3 immunostaining. Retinal redox status was estimated by measuring retinal superoxide dismutase, catalase, glutathione, and malondialdehyde levels using enzyme-linked immuosorbent assay. Histopathological examination showed significantly improved retinal and optic nerve morphology in TAU-treated groups. Morphometric examination showed that TAU pre-treatment provided marked protection against ET-1 induced damage to retina and optic nerve. In accordance with the morphological observations, immunostaining for caspase showed a significantly lesser number of apoptotic retinal cells in the TAU pre-treatment group. The retinal oxidative stress was reduced in all TAU-treated groups, and particularly in the pre-treatment group. The findings suggest that treatment with TAU, particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1 and hence prevents the changes in the morphology of retina and optic nerve. The protective effect of TAU against ET-1 induced retinal and optic nerve damage is associated with reduced retinal oxidative stress.
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 (ET-1) into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.
基金supported by the National Natural Science Foundation of China(No.81070067)
文摘The effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin on the enhanced hypoxia induced factor-let (HIF-lct) and endothelin-1 (ET-1) expression, elevated systolic blood pressure under chronic intermittent hypoxia (CIH) condition and its action mechanism were investigated. Thirty healthy 8-week old Sprague-Dawley (SD) male rats were randomly divided into three groups (n=10 each): sham group, CIH group, and apocynin-treated CIH group. Tail artery systolic blood pressure was measured by tail-cuff method. Real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression of HIF-lu and ET-1 in the carotid body, and the HIF-1a protein expression was examined by using Western blotting. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using colorimetric method. In addition, the plasma ET-1 and HIF-1a levels were measured by using enzyme-linked immunosorbent assay. It was found that CIH exposure was associated with increased MDA levels, and apo- cynin-treated CIH animals showed reduction in MDA levels. Apocynin treatment prevented CIH-induced hypertension as well as CIH-induced decrease in SOD. The increases of HIF-1a and ET-1 mRNA along with HIF-la protein expression in the carotid body, and elevated circulating HIF-1a and ET-1 levels were observed in CIH-exposed animals. Treatment with apocynin significantly decreased the ET-1 mRNA, HIF-lct protein expression and circulating HIF-la level in CIH-exposed animals, and there was no statistically significant difference in the HIF-lu mRNA expression between CIH group and apo- cynin-treated group. These results indicated that apocynin alleviated CIH-induced hypertension by inhibiting NADPH oxidase, further leading to the reduced vasoconstrictor ET-1 level and oxidative stress. HIF-1a/ET-1 system signal pathway may interact with CIH-induced NADPH oxidase-dependent oxidative stress. Inhibition of NADPH oxidase activity may hopefully serve as a useful strategy for prevention and treatment of obstructive sleep apnea hypopnea syndrome-induced hypertension.
文摘Objective: To compare the levels of p38 mitogen-activated protein kinase (MAPK), soluble endoglin and endothelin-1 in the serum of patients with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and normal pregnancies. Methods: This study was an observational analytic cross-sectional study performed at Wahidin Sudirohusodo Hospital, Makassar, Indonesia, in the period of 5th February 2016 to 20th January 2017. P38 MAPK, soluble endoglin and endothelin-1 levels of patients with normal pregnancies, severe preeclampsia and HELLP syndrome were measured by enzyme-linked immunoabsorbentassay technique, using kits of human soluble endoglin, endothelin-1 and p38 MAPK, Quantikine immunoassay: R&D System Inc. Results: Level of serum p38 MAPK in HELLP syndrome group was higher than in severe preeclampsia and normal pregnancy groups. Soluble endoglin and endothelin-1 levels in pregnancies with severe preeclampsia and HELLP syndrome were higher than normal pregnancy but there was no significant difference between these two groups (P>0.05). Levels of p38 MAPK, soluble endoglin and endothelin-1 also had a positive linear correlation with systolic and diastolic blood pressures (P<0.05). Conclusions: P38 MAPK in serum may be a marker for evidence of the severe hypoxia and its application may be considered for the diagnosis of HELLP syndrome.
基金Foundation:Directorate General of Higher Education(DGHE),National Education Ministry Republic of Indonesia
文摘AIM: To evaluate effect of hypertension on retinal ganglion cell(RGC) apoptosis, intraocular pressure(IOP),and the activation of endothelin-1(ET-1) signaling pathway in central retinal artery(CRA) in rats.METHODS: The experimental study was performed on20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate(DOCA)10 mg/kg twice a week and administered 0.9% Na Cl solution daily for 2, 6, and 10 wk. Blood pressure(BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, e NOS, ET-1 receptor A(ETRA), ET-1receptor B(ETRB), and phosphorylated myosin light chain kinase(MLCK), and caldesmon(Ca D) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS: BP significantly increased in all of the hypertension groups compared to control(P =0.001).Peak IOP elevation(7.78±4.14 mm Hg) and RGC apoptosis(576.15±33.28 Au) occurred on 2wk of hypertension. ET-1expression(1238.6±55.1 Au) and e NOS expression(2814.2±70.7 Au) were found highest in 2wk of hypertension,although the ratio of ET-1/e NOS decreased since 2wk.ETRAreached peak expression in 10 wk of hypertension(1219.4 ±6.3 Au), while ETRBsignificantly increased only in 2 weeks group(1069.2 ±9.6 Au). The highest MLCK expression(1190.09±58.32 Au), Ca D(1670.28±18.36 Au)were also found in 2wk of hypertension.CONCLUSION: Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension.
基金supported by Natural Science Foundation of China(81470466)。
文摘Objective To investigate whether plasma big endothelin-1(ET-1) predicts ventricular arrythmias(VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator(ICD) indication patigents. Methods In total, 207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analyzed. The cohort was divided into three groups according to baseline plasma big ET-1 tertiles: tertile 1(< 0.38 pmol/L, n = 68), tertile 2(0.38–0.7 pmol/L, n = 69), and tertile 3(> 0.7 pmol/L, n = 70). The primary endpoints were VAs. The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation. Results During a mean follow-up period of 25.6 ± 13.9 months, 38(18.4%) VAs and 78(37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class(r = 0.165, P = 0.018), serum creatinine concentration(Scr;r = 0.147, P = 0.034), high-sensitivity C-reactive protein(hs-CRP;r = 0.217, P = 0.002), Lg NT-pro BNP(r = 0.463, P < 0.001), left ventricular end diastolic diameter(LVEDD;r = 0.234, P = 0.039) and negatively correlated with left ventricular ejection fraction(LVEF;r =-0.181, P = 0.032). Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events(P < 0.05). In multivariate Cox regression models, big ET-1 was an independent risk factor for VAs(hazard ratio(HR) = 3.477, 95% confidence interval(CI): 1.352–8.940, P = 0.010, tertile 2 vs. tertile 1;HR = 4.112, 95% CI: 1.604–10.540, P = 0.003, tertile 3 vs. tertile 1) and end-stage events(HR = 2.804, 95% CI: 1.354–5.806, P = 0.005, tertile 2 vs. tertile 1;HR = 4.652, 95% CI: 2.288–9.459, P < 0.001, tertile 3 vs. tertile 1). Conclusions In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.
文摘The present study investigated a possible mechanism for endogenous endothelin-1 (ET-1) regulation of atrial natriuretic peptide (ANP) secretion in isolated perfused acute hypoxic rabbit atria. Acute hypoxia significantly enhanced the release of ET-1 and the expression of the ET receptor (ETR) type A and B (ETR<sub>A</sub> and ETR<sub>B</sub>) in atrial tissues, with a concomitant increase in ANP secretion. The ETR<sub>A</sub> or ETR<sub>B</sub> antagonist, BQ123 (0.3 μmol/L) or BQ788 (0.3 μmol/L), respectively attenuated hypoxia-induced ANP secretion. Both antagonists significantly attenuated the levels of hypoxiainduced atrial phosphorylated (p)-extracellular signal-regulated kinase (ERK) and p-protein kinase B (Akt). The ERK and Akt inhibitors, PD098059 (30 μmol/L) and LY294002 (30 μmol/L), respectively mimicked the effect of the ETR antagonists. These results demonstrated that acute hypoxia- mediated atrial ET-1 regulated ANP secretion through ETR and the subsequent mitogenactivated protein kinase (MAPK)/ERK and ETR-phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. These pathways may mediate atrial endocrine functions under hypoxic conditions.
基金The authors gratefully acknowledge the support of this work by the National Natural Science Foundation of China(based on the Systems Biology of Acupuncture on Irritable Early Hypertension Control Mechanism and Intervention Study Targets Research,no.81072861).
文摘Objective:To explore the protective effect of acupuncture against myocardial injury in rats with stress-induced prehypertension (SIPH) by observing the genetic expression of myocardial endothelin-1 (ET-1) and atrial natriuretic peptide (ANP).Methods:Thirty-six Wistar rats were randomized into three groups:the control group,model group,and model + acupuncture (AP) group (n =12 rats per group).During the 11-day modeling period,the model group and the model + AP group experienced plantar electric stimulation in combination with noise exposure,and daily acupuncture intervention was applied simultaneously in the model + AP group;the control group did not experience modeling or acupuncture.Systolic pressure (SP) was measured the day before modeling began,and on the 3rd,5th,7th,9th,and 11th day after modeling initiation.On the 12th day,histopathological observation of the left ventricle was made with hematoxylin-eosin staining and quantitative genetic expression of myocardial ET-1,and ANP was tested by quantitative real-time polymerase chain reaction (PCR).Results:SP was higher in the model group than the control group on the 3rd,5th,7th,9th,and 11th days (all P <.01).SP in the model + AP group was lower than that in the control group on the 5th and 7th days (respectively,P =.008,P =.002) and on the 9th and 11th days (P =.029,P =.039).Hematoxylin-eosin staining showed normal myocardial cellular structure in the control group.The model group showed disordered arrangement of cardiac cells with morphological changes in some nuclei,including enlargement or dissolution;there was also infiltration of inflammatory cells and proliferation of collagen fibers.In the model + AP group,most of the myocardial cells were normally structured,and only part of the cells had morphological changes with enlarged nuclei or dissolution.Real-time PCR showed that expression of ET-1 and ANP mRNA in the model group was greater than the control group (respectively,P =.024,P =.000101).The model + AP group had lower expression of ET-1 and ANP mRNA compared with the model group (respectively,P =.033,P =.043).Conclusion:Acupuncture may lower blood pressure and downregulate the genetic expression of myocardial ET-1 and ANP in SIPH rats,suggesting a protective effect of acupuncture against myocardial damage.
文摘BACKGROUND: Several studies have confirmed that endothelin and endorphin are involved in the occurrence of cerebral vasospasm. However, the correlation of these factors to acute cerebral infarction-related risk factors needs to be confirmed. OBJECTIVE: To detect endothelin-1 (ET-1) and beta-endorphin (β -EP) levels in plasma of patients with acute cerebral infarction, and to analyze the correlations of these factors to smoking, alcohol abuse, hypertension, diabetes mellitus, diseased region, diseased degree, gender, and other factors related to acute cerebral infarction. DESIGN: A case-control observation. SETTING: First Department of Neurology, Guangdong Hospital of Traditional Chinese Medicine; Department of Neurology, Second Affiliated Hospital of Sun Yat-sen University. PARTICIPANTS: Sixty-nine inpatients with acute cerebral infarction were admitted to the Department of Neurology, Second Affiliated Hospital of Sun Yat-sen University (March 2003-January 2004) and First Department of Neurology, Guangdong Hospital of Traditional Chinese Medicine (March July 2004) and recruited for this study. All 69 inpatients corresponded to the diagnosis criteria of acute cerebral infarction, formulated in the National Working Conference of Cerebrovascular Disease in 1998, and were confirmed as acute cerebral infarction by CT/MRI. The patient group consisted of 35 males [(644- 12) years old] and 34 females[ (674- 13 ) years old]. Among them, 9 patients were smokers, 7 were alcohol users, 48 had a history of hypertension, and 16 had a history of diabetes mellitus. CT/MRI examinations revealed that 35 patients presented with left focus sites, 11 with right ones and 23 with bilateral ones. Following attack, 24 patients had Barthel Index Scale grading 〈 40 points, 21 patients 40-50 points, and 24 patients 〉 60 points. An additional 59 healthy individuals, who received health examinations simultaneously, were included as controls. Among the control subjects, there were 37 males [(62±10) years old] and 22 females [(65±11) years old]. Among them, 7 patients were smokers, and 6 were alcohol users. All controls had no history of stroke, hypertension, or diabetes mellitus. Informed consents of laboratory measurements were obtained from all subjects, and this study was approved by the Hospital Ethics Committee. METHODS: ① Following admission, all subjects were scored by Barthel Index Scale (BIS) and Hamilton Depression Scale. Meanwhile, hypertension, diabetes mellitus, gender, smoking, drinking, and other conditions were recorded. CT/MRI examination was conducted to identify the focus site.②On the 2^nd day after admission, ET-1 and β -EP plasma levels were measured with an automatic ET-1 and β -EP analysis kit. MAIN OUTCOME MEASURES: ET-1 and β -EP plasma levels and their correlation to acute cerebral infarction-related factors. RESULTS: Sixty-nine patients with acute cerebral infarction, and an additional 59 healthy individuals participated in the final analysis. β ET-1 [(63.80±27.65) ng/L vs. (46.50±9.36) ng/L, P 〈 0.05] and β - EP [(94.18±33.94) mg/L vs. (51.87±23.43) mg/L, P 〈 0.05] levels of the patient group were obviously higher than respective values of the control group. ② The ET-1 and β -EP levels of patients with cerebral infarction did not correlate to hypertension, diabetes mellitus, BIS, depression, cerebral infarct focus, disease course, gender, smoking or drinking (P 〉 0.05). CONCLUSION: The ET-I and β-EP levels of patients with acute cerebral infarction increased, but they were not obviously associated with disease course, blood pressure, blood glucose, BIS, or other common cerebral infarction-related factors.
基金Supported by National Natural Science Foundation of China,No.81370496 and No.81873647Youth Program of National Natural Science Foundation of China,No.81600059。
文摘BACKGROUND Previous evidence has implied that obesity is an independent risk factor for developing cancer.Being closely related to obesity,type 2 diabetes mellitus provides a suitable environment for the formation and metastasis of tumors through multiple pathways.Although bariatric surgeries are effective in preventing and lowering the risk of various types of cancer,the underlying mechanisms of this effect are not clearly elucidated.AIM To uncover the role and effect of sleeve gastrectomy(SG)in preventing lung cancer in obese and diabetic rats.METHODS SG was performed on obese and diabetic Wistar rats,and the postoperative transcriptional and translational alterations of the endothelin-1(ET-1)axis in the lungs were compared to sham-operated obese and diabetic rats and age-matched healthy controls to assess the improvements in endothelial function and risk of developing lung cancer at the postoperative 4 th,8 th,and 12 th weeks.The risk wasalso evaluated using nuclear phosphorylation of H2 A histone family member X as a marker of DNA damage(double-strand break).RESULTS Compared to obese and diabetic sham-operated rats,SG brought a significant reduction to body weight,food intake,and fasting blood glucose while improving oral glucose tolerance and insulin sensitivity.In addition,ameliorated levels of gene and protein expression in the ET-1 axis as well as reduced DNA damage indicated improved endothelial function and a lower risk of developing lung cancer after the surgery.CONCLUSION Apart from eliminating metabolic disorders,SG improves endothelial function and plays a protective role in preventing lung cancer via normalized ET-1 axis and reduced DNA damage.
文摘To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia11y reported by various authors. We have performed investigations in anesthetized Sprague-Dawley rats- Intracisternal injection (i. c. ) of ET-l (10-11, 10-10, 10-9 mol/kg) could induce acute dose-dependent CVS, furthermore, the highest dose of ET-l (lO-’ mo1/kg) had a biphasic response in CVS of a 24-hour duration. However, the CVS by ET-1 (10-9 mol/kg) could be prevented effectively by previous i. c. of BQ-123 in a dose-dependent manner (10-9, 10-8, 10-7 mol/kg), of which the i. c- of BQ-123 (10-7mol/kg) could abolish the CVS completely. i. c. of BQ-123 (10-7 mol/kg) before SAH induced by a single i. c, of 150 pl autologous fresh blood directly to the Willis circle cou1d prevent the following CVS largely, which was a biphasic response and long-lasting (duration of 72 h). We conclude that subarachnoid application of ETA-receptor antagonist can effecti vely prevent CVS induced by ET-1 and SAH, and ET-1 may be the major mediator responsible for the CVS following SAH.