AIM: To investigate the effect of Helicobacter pylori eradication on endothelin-1 (ET-1) and nitric oxide (NO) in duodenal ulcer (DU) patients. METHODS: Sixty-six Hpylori-infected active DU patients were consecutively...AIM: To investigate the effect of Helicobacter pylori eradication on endothelin-1 (ET-1) and nitric oxide (NO) in duodenal ulcer (DU) patients. METHODS: Sixty-six Hpylori-infected active DU patients were consecutively enrolled to receive one-week triple therapy (rabeprazole, amoxicillin and metronidazole) and then one-month rabeprazole therapy. They were asked back to determine ulcer and Hpylori status using endoscopy one month later. Thirty-seven healthy controls (H pylori +/-:17/20) were enrolled for comparison. Blood samples were collected in each visit to measure plasma ET-1 and nitrate/nitrite levels using an enzyme immunoassay kit. RESULTS: Sixty DU patients finished trial per protocol. The ulcer healing and Hpylori-eradication rates were 86.7% and 83.3%, respectively. Plasma ET-1 level in DU patients was higher than that of Hpylori-negative and positive controls (3.59±0.96 vs0.89±0.54 vs0.3±0.2 pg/mL,P<0.01), while nitrate/nitrite levels among them were also significantly different (8.55±0.71 vs5.27±0.68 vs 6.39±0.92 μmol/L, P<0.05). H pylori eradication diminished ET-1 levels (3.64±0.55 vs2.64±0.55 pg/mL, P<0.01) but elevated nitrate/ nitrite level (8.16±0.84 vs11.41±1.42 umol/L,P<0.05). CONCLUSION: Both plasma ET-1 and nitrate/nitrite levels increase in active DU patients. After an effective H pylori eradication, DU healing is associated with diminished blood ET-1 level and elevated nitrate/nitrite level.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
To study the relationship between the disturbance of nitric oxide/endothelin-1 (NO/ET-1) and the hepatic ischemia/reperfusion (I/R) injury as well as the regulation of the NO/ET-1 system by the hepatic ischemic precon...To study the relationship between the disturbance of nitric oxide/endothelin-1 (NO/ET-1) and the hepatic ischemia/reperfusion (I/R) injury as well as the regulation of the NO/ET-1 system by the hepatic ischemic preconditioning (IPC), the changes of the NO/ET-1 system and their relationship with the hepatic I/R injury were compared between the I/R group and the IPC+I/R group in a rat hepatic I/R model. 2 h after reperfusion, the liver tissues were examined for expressed inducible nitric oxide synthase (iNOS) mRNA by RT-PCR. In the acute phase of hepatic reperfusion, the ratio of NO/ET-1 was reduced, which was due to the significant reduction of NO - 2/NO - 3 (the metabolic product of NO) and significant elevation of ET-1 in the blood plasma. The content of ALT, AST, LDH and TNF-α in blood plasma, and level of MDA in liver tissue were increased but ATP in liver tissue was reduced, and the hepatic damage was deteriorated. The protection of the hepatic IPC was associated with the elevated ratio of NO/ET-1 caused by the elevation of NO - 2/NO - 3, and reduction of ET-1 as well. No iNOS mRNA was detected in the liver tissues. It was concluded that hepatic I/R injury was related to the disturbance of NO/ET-1. The protection of the hepatic IPC in the acute phase might be mediated by its regulation of NO/ET-1 system. The cNOS rather than the iNOS generated the NO in this scenario.展开更多
Objective:To study the effect of smoking on EA and NOS expression as well as NO and ET-1 content in gingival tissue of patients with chronic periodontitis.Methods: Patients diagnosed with periodontitis in our hospital...Objective:To study the effect of smoking on EA and NOS expression as well as NO and ET-1 content in gingival tissue of patients with chronic periodontitis.Methods: Patients diagnosed with periodontitis in our hospital between May 2013 and March 2016 were selected to screen 72 cases of smokers and 80 cases of non-smokers who were enrolled in smoking group and non-smoking group respectively, periodontal tissue was collected to detect the expression of EA, NOS and NLRP3 inflammasome, and gingival crevicular fluid was collected to detect the content of ET-1, NO, inflammatory factors and MMPs.Results:EA expression and ET-1 content in gingival tissue of smoking group were significantly higher than those of non-smoking group while NOS expression and NO content in gingival tissue were significantly lower than those of non-smoking group;NLRP3, ASC, Caspase-1, IL-1β and IL-18 expression in gingival tissue of smoking group were significantly higher than those of non-smoking group, and IL-1β, IL-18, TNF-α, IFN-γ, MMP1, MMP8 and MMP13 content in gingival crevicular fluid were significantly higher than those of non-smoking group;NLRP3, ASC, Caspase-1, IL-1β and IL-18 expression as well as IL-1β, IL-18, TNF-α, IFN-γ, MMP1, MMP8 and MMP13 content were positively correlated with EA and ET-1, and negatively correlated with NOS and NO.Conclusion:Smoking can cause increased EA and ET-1 as well as decreased NOS and NO in gingival tissue of patients with chronic periodontitis, thus adjusting the expression of NLRP3 inflammasome and MMPs to periodontal tissue inflammation and structure damage.展开更多
Objective:To observe effects of Liandou Qingmai Recipe(连豆清脉方) on endothelin-1(ET-1),nitric oxide(NO),interleukin-6(IL-6) and IL-10 levels in patients with coronary heart disease.Methods:Total 101 cases with coron...Objective:To observe effects of Liandou Qingmai Recipe(连豆清脉方) on endothelin-1(ET-1),nitric oxide(NO),interleukin-6(IL-6) and IL-10 levels in patients with coronary heart disease.Methods:Total 101 cases with coronary heart disease were randomly divided into a treatment group(n=45) treated by Liandou Qingmai Recipe and a standard treatment group(control group,n=56),with a normal group of 16 health persons set up.Changes of ET-1,NO,IL-6 and IL-10 levels were measured before treatment and after treatment for two weeks.And the data were analyzed by SPSS 16.0 statistic software.Results:Before treatment,the levels of ET-1,IL-6 and IL-10 levels were significantly higher and NO was significantly lower in the patients with coronary heart disease than those in the normal group(90.7±12.7 ng/L vs 41.8±13.5 ng/L,9.17±0.18 ng/L vs 1.10±0.08 ng/L,1.94±0.26 ng/L vs 1.09±0.06 ng/L,and 92.2±17.7 μmol/L vs 124.5±27.2 μmol/L;all P<0.05),with no significant differences in the levels of ET-1,NO,IL-6 and IL-10 between the treatment group and the control group(P>0.05);After treatment,ET-1 and IL-6 significantly decreased in the treatment group and the control group,and NO increased in the treatment group;And IL-6 level was significantly lower and NO level was higher in the treatment group than those in the control group(4.48±1.22 ng/L vs 5.13±1.85 ng/L,117.4±22.3 μmol/L vs 92.4±17.1 μmol/L;both P<0.05);There was a positive correlation between IL-6 and IL-10,and a negative correlation between NO and IL-10(r=0.142,r=-0.152;both P<0.05).Conclusion:Liandou Qingmai Recipe can decline IL-6,IL-10 and ET-1 levels,and raise NO level in patients with coronary heart disease on the basis of standard treatment,so as to inhibit endothelial inflammatory response,improve vascular endothelial function,with stronger anti-AS action;And vascular endothelial lesion is related with inflammatory response.展开更多
OBJECTIVE: To observe the influence of moxibustion temperature on blood lipids, endothelin-1(ET-1), nitric oxide(NO), and ET-1/NO in hyperlipidemia patients. METHODS: Forty-two primary hyperlipidemia patients we...OBJECTIVE: To observe the influence of moxibustion temperature on blood lipids, endothelin-1(ET-1), nitric oxide(NO), and ET-1/NO in hyperlipidemia patients. METHODS: Forty-two primary hyperlipidemia patients were randomly divided into two groups of 21 and treated with moxibustion at different temperatures. Moxibustion was performed with the moxa roll 2.5-3.0 cm from the skin in the treatment group and 4 cm in the control group, 10 min per point, once every other day. Skin temperature was precisely measured with a thermometer during moxibustion. After a 12-week treatment, seven measurements of blood lipids, ET-1, and NO were recorded. RESULTS: Total cholesterol and triglyceride, were lower in the treatment group than in the control group(P0.05). Serum ET-1 and ET-1/NO was obvi-ously lowered in the treatment group(P0.001). Moxibustion regulated NO and ET-1/NO in the treatment group much better than in the control group. CONCLUSION: Moxibustion can regulate blood lipids and clear blood vessels. Moxibustion at 45℃has a better effect than moxibustion at 38℃ on regulating blood lipids and protecting vascular endothelial function, indicating that suitable temperature influences the curative effect of moxibustion.展开更多
The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin?1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n...The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin?1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (PAPm) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FIO2 = 0.10) was 25 ?3.1 kPa and 68.7 ?10.2 kPa.s / L respectively. IG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of PAPm and PVR during hypoxic ventilation to 36.6 ?4.7 kPa and 158.4 ?25 kPa.s / L and its effect lasted for 2-3 hours. Meanwhile, plasma endothelin? level in the femoral artery increased by 20.9+ 7.1, 25.6?7.7, 28.6?7.9 pg / ml at the 60 th, 120th, 180th minute after the injection of L-NAME respectively (P<0.05 vs hypoxic control before the injection). In cultured endothelial cells from umbilical veins, endothelin-1 level of culture medium in control group was 35.1 ?.9 pg / 105 cells /ml (n=9). L-NAME increased endothelin-1 level to 42.8 ?4.9pg / 105 cells / ml (n = 9, P < 0.05) in case of 10-11 mol / L and to 43.0+ 4.7 pg / 105 cells / ml in case of 10 -7 mol/L (n=9, F<0.05). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin? in vivo and in cultured vascular endothelial cells.展开更多
Background Nitric oxide (NO) plays an important role in acute lung injury (ALl), acute respiratory distress syndrome (ARDS), and in ventilator-induced lung injury (VILI). A change in the balance of endothelin...Background Nitric oxide (NO) plays an important role in acute lung injury (ALl), acute respiratory distress syndrome (ARDS), and in ventilator-induced lung injury (VILI). A change in the balance of endothelin-1 (ET-1) and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model. Methods Models of oleic acid induced ALl were established in dogs; these models were then randomized into three groups undergone different tidal volume (VT) mechanical ventilation, which included a VT6 group (VT equaled to 6 ml/kg body weight, positive end expiratory pressure (PEEP) equaled to 10 cmH20, n=-6), a VT10 group (VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH20, n=-4) and a VT20 group (VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH20, n=-6) for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial. Results PaO2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALl models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation (P 〈0.05) while the serum NO levels were similar in the three groups (all P 〉0.05). There was no significant difference in serum ratio of ET-1/NO between any two out of three groups (P 〉0.05), although there was a significant positive relationship between serum ET-1 and serum NO (r=0.80, P 〈0.01). The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group (both P 〈0.05) while there was no significant difference in lung NO levels between two groups (P〉0.05). In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation (P 〈0.05) as there was a significant positive relationship between ET-1 and NO in the lung (r=0.54, P 〈0.05). Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.展开更多
Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals,the variability highlighted by differing genetic haplotypes.Despite the abundance of reports of...Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals,the variability highlighted by differing genetic haplotypes.Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase(eNOS)and endothelin-1(ET-1)genes,the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear.To deconvolute their potential significance among African Americans with sickle cell disease,we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease(n Z 331)and control(n Z 379)groups,with a polymerase echain reaction restriction fragment length polymorphism assay.We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups.eNOS homozygote mutants,which had been shown to have clinical significance elsewhere,showed no statistical significance in our study.On the other hand,and contrary to previous report among Africans with sickle cell disease,the endothelin-1 homozygous mutant variant showed significant difference in genotypic(p Z 2.84E-12)and allelic frequencies(p Z 2.20E-16)between groups.The most common haplotype is the combination of T786C homozygote wildtype variant with homozygote mutant variants of G5665T(ET-1)and Glu298Asp(eNOS).These results show that endothelin-1(rs5370)polymorphism,rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease.This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications.展开更多
AIM:To establish a rat ethanol gastritis model,we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis.METHODS:One hundred...AIM:To establish a rat ethanol gastritis model,we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis.METHODS:One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups:normal control group,undergoing gastric perfusion of normal saline(NS) by gastrogavage;model control group and 2 model therapy groups that underwent gastric perfusion with ethanol(distillate spirits with 56% ethanol content) by gastrogavage for 4 wk.Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups,while the same amount of NS,instead of geranylgeranylacetone was used in that model control group.The rats were then sacrificed and stomachs were removed.The injury level of the gastric mucosa was observed by light and electron microscopy,and the levels of prostaglandin 2(PGE 2),endothelin-1(ET-1) and nitric oxide(NO) were measured by radioimmunoassay and the Griess method.RESULTS:The gastric mucosal epidermal damage score(EDS;4.5) and ulcer index(UI;12.0) of the model control group were significantly higher than that of the normal control group(0 and 0 respectively,all P = 0.000).The gastric mucosal EDS and UI of the 2 model therapy groups(EDS:2.5 and 2.0;UI:3.5 and 3.0) were significantly lower than that of the model control group(all P < 0.01).There was no statistically significant difference between the low-dose and high-dose model therapy groups.The expression value of plasma ET-1 of the model control group was higher than that of the normal control group(P < 0.01) and the 2 model therapy groups(all P < 0.01).The expression values of gastric mucosal PGE 2 and serum NO of the model control group were lower than those of the normal control group(all P < 0.05) and the 2 model therapy groups(all P < 0.05).The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group(all P < 0.01) and the 2 model therapy groups(all P < 0.05).Scanning and transmission electron microscopy observation showed that in the model control group,the epithelial junctions were vague,the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group.However,in the 2 model therapy groups,damage to the intercellular joints and organelles was ameliorate relative to the model control group.CONCLUSION:Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion.The mechanism could be related to regulation of ET-1,NO and PGE 2.展开更多
Objective To explore the correlation between endothelia cells activation and cytokines (ET-1, NO) levels in patients with pulmonary hypertension (PH), and to discuss their roles in the development of PH. Methods Twent...Objective To explore the correlation between endothelia cells activation and cytokines (ET-1, NO) levels in patients with pulmonary hypertension (PH), and to discuss their roles in the development of PH. Methods Twenty patients with simple ventricular septal defect (VSD) were chosen as controls, and 30 patients with PH were studied. Plasma levels of ET-1 and NO were measured by radioimmunoassay or colorimetric method. Before cardiopulmonary bypass was established, the specimens from right lung were fixed with formaldehyde solution, embedded with paraffin and stained by SP immunohistochemistry. Intercellular adhesion molecule-1 (ICAM-1) expression was measured through the determination of the light density with computer imaging technology. Results Compared with that of the patients with simple VSD, the light density of ICAM-1 and plasma level of ET-1 increased in patients with PH; but plasma level of NO decreased (P<0.05). Positive correlation was observed between ICAM-1 and ET-1/NO (P<0.05). Conclusion Endothelia cells activation and imbalance of ET-1/NO might play an important role in the development of PH.展开更多
Background:Reversibility of pulmonary hypertension(PH)is closely related to the treatment options for and prognosis of children with congenital heart disease.Objective:We combined patient-specific clinical features in...Background:Reversibility of pulmonary hypertension(PH)is closely related to the treatment options for and prognosis of children with congenital heart disease.Objective:We combined patient-specific clinical features including diagnosis,age and echocardiographic results,and biomarkers of pulmonary vascular dysfunction to explore the noninvasive methods that can be used to accurately evaluate the reversibility of pulmonary hypertension in congenital heart disease(PH-CHD).Methods:Based on the preoperative systolic pulmonary arterial pressure(sPAP),70 CHD patients were divided into normal,PH-CHD suspected,and confirmed groups.Additionally,biomarkers of circulating endothelial cells(CECs),endothelin-1(ET-1),and endothelial nitric oxide synthase(eNOS)were detected.Patients were categorized into reversible(RPH)and irreversible(IRPH)groups according to the sPAP 6 months after surgery.Risk stratification was performed according to the clinical features and biomarkers.Results:CECs and ET-1 levels in the confirmed group were significantly higher.eNOS was higher in the confirmed and suspected groups than that in the normal group.CECs in the IRPH group were significantly higher compared to the RPH group.No such intergroup differences were observed with respect to ET-1 and eNOS levels.The ROC curve showed that the risk stratification was of high diagnostic value to evaluate reversibility.Conclusion:The CECs,eNOS,and ET-1 were closely related with PH-CHD.CECs and risk stratification have high practical value in assessing the reversibility of PH-CHD.展开更多
For the treatment of brain ischemia using acupuncture, the needle is predominantly inserted into muscular layers and deep tissue. However, few studies have investigated the outcomes of shallow needling. The present st...For the treatment of brain ischemia using acupuncture, the needle is predominantly inserted into muscular layers and deep tissue. However, few studies have investigated the outcomes of shallow needling. The present study established middle cerebral artery occlusion models in rats using the thrombosis method. Shallow needling and conventional needling at the bilateral Neiguan (PC 6) and Gongsun (SP 4) acupoints improved neurological function of middle cerebral artery occlusion rats, increased the expression of the anti-apoptotic Bcl-2, inhibited the expression of the pro-apoptotic Bax, and reduced the expression of the vasoactive substances nitric oxide synthase and endothelin-1. However, these changes were more pronounced in the shallow needling group, indicating that shallow needling is more effective in inhibiting brain ischemic injury.展开更多
OBJECTIVE:To observe the effects of Liandouqingmai Recipe on life quality and vascular endothelial injury in patients with coronary heart disease.METHODS:Capitalized 101 patients with coronary heart disease were rando...OBJECTIVE:To observe the effects of Liandouqingmai Recipe on life quality and vascular endothelial injury in patients with coronary heart disease.METHODS:Capitalized 101 patients with coronary heart disease were randomly divided into a treatment group(n=45) treated with Liandouqingmai Recipe and a standard treatment group(control group,n=56).A normal group of 16 healthy persons was additionally set up.Changes in ET-1 and NO levels were measured and Seatle Angina Questionnaire(SAQ) was adopted in studying life quality before and after treatment for two weeks.The data were analyzed with SPSS 16.0 statistic software.RESULTS:The average level of ET-1 in the normal group was lower and NO higher than that of patients with coronary heart disease.There was no significant difference in the average level of ET-1 and NO and in the scores of SAQ [physical limitation(PL),pngina stability(AS),apngina frequency(AF),treatment satisfaction(TS) and disease perception(DP)] between the two groups before treatment(P>0.05).But after treatment,the scores of SAQ(PL,AS,AF,TS,DP) and NO level were higher than those in the control group,and ET-1 average level in the treatment group was lower than that in the control group.The negative relations between PL and ET-1 and between AF and ET-1 were found in this study.CONCLUSION:Liandouqingmai Recipe can raise scores of SAQ and NO level and decline ET level in patients with coronary heart disease on the basis of convertional standard treatment,thus improving vascular endothelial function and life quality.Life quality is related to vascular endothelial function.展开更多
基金Supported by the Research Foundation of Digestive Medicine,Taiwan, China
文摘AIM: To investigate the effect of Helicobacter pylori eradication on endothelin-1 (ET-1) and nitric oxide (NO) in duodenal ulcer (DU) patients. METHODS: Sixty-six Hpylori-infected active DU patients were consecutively enrolled to receive one-week triple therapy (rabeprazole, amoxicillin and metronidazole) and then one-month rabeprazole therapy. They were asked back to determine ulcer and Hpylori status using endoscopy one month later. Thirty-seven healthy controls (H pylori +/-:17/20) were enrolled for comparison. Blood samples were collected in each visit to measure plasma ET-1 and nitrate/nitrite levels using an enzyme immunoassay kit. RESULTS: Sixty DU patients finished trial per protocol. The ulcer healing and Hpylori-eradication rates were 86.7% and 83.3%, respectively. Plasma ET-1 level in DU patients was higher than that of Hpylori-negative and positive controls (3.59±0.96 vs0.89±0.54 vs0.3±0.2 pg/mL,P<0.01), while nitrate/nitrite levels among them were also significantly different (8.55±0.71 vs5.27±0.68 vs 6.39±0.92 μmol/L, P<0.05). H pylori eradication diminished ET-1 levels (3.64±0.55 vs2.64±0.55 pg/mL, P<0.01) but elevated nitrate/ nitrite level (8.16±0.84 vs11.41±1.42 umol/L,P<0.05). CONCLUSION: Both plasma ET-1 and nitrate/nitrite levels increase in active DU patients. After an effective H pylori eradication, DU healing is associated with diminished blood ET-1 level and elevated nitrate/nitrite level.
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.
文摘To study the relationship between the disturbance of nitric oxide/endothelin-1 (NO/ET-1) and the hepatic ischemia/reperfusion (I/R) injury as well as the regulation of the NO/ET-1 system by the hepatic ischemic preconditioning (IPC), the changes of the NO/ET-1 system and their relationship with the hepatic I/R injury were compared between the I/R group and the IPC+I/R group in a rat hepatic I/R model. 2 h after reperfusion, the liver tissues were examined for expressed inducible nitric oxide synthase (iNOS) mRNA by RT-PCR. In the acute phase of hepatic reperfusion, the ratio of NO/ET-1 was reduced, which was due to the significant reduction of NO - 2/NO - 3 (the metabolic product of NO) and significant elevation of ET-1 in the blood plasma. The content of ALT, AST, LDH and TNF-α in blood plasma, and level of MDA in liver tissue were increased but ATP in liver tissue was reduced, and the hepatic damage was deteriorated. The protection of the hepatic IPC was associated with the elevated ratio of NO/ET-1 caused by the elevation of NO - 2/NO - 3, and reduction of ET-1 as well. No iNOS mRNA was detected in the liver tissues. It was concluded that hepatic I/R injury was related to the disturbance of NO/ET-1. The protection of the hepatic IPC in the acute phase might be mediated by its regulation of NO/ET-1 system. The cNOS rather than the iNOS generated the NO in this scenario.
文摘Objective:To study the effect of smoking on EA and NOS expression as well as NO and ET-1 content in gingival tissue of patients with chronic periodontitis.Methods: Patients diagnosed with periodontitis in our hospital between May 2013 and March 2016 were selected to screen 72 cases of smokers and 80 cases of non-smokers who were enrolled in smoking group and non-smoking group respectively, periodontal tissue was collected to detect the expression of EA, NOS and NLRP3 inflammasome, and gingival crevicular fluid was collected to detect the content of ET-1, NO, inflammatory factors and MMPs.Results:EA expression and ET-1 content in gingival tissue of smoking group were significantly higher than those of non-smoking group while NOS expression and NO content in gingival tissue were significantly lower than those of non-smoking group;NLRP3, ASC, Caspase-1, IL-1β and IL-18 expression in gingival tissue of smoking group were significantly higher than those of non-smoking group, and IL-1β, IL-18, TNF-α, IFN-γ, MMP1, MMP8 and MMP13 content in gingival crevicular fluid were significantly higher than those of non-smoking group;NLRP3, ASC, Caspase-1, IL-1β and IL-18 expression as well as IL-1β, IL-18, TNF-α, IFN-γ, MMP1, MMP8 and MMP13 content were positively correlated with EA and ET-1, and negatively correlated with NOS and NO.Conclusion:Smoking can cause increased EA and ET-1 as well as decreased NOS and NO in gingival tissue of patients with chronic periodontitis, thus adjusting the expression of NLRP3 inflammasome and MMPs to periodontal tissue inflammation and structure damage.
基金supported by Bureau of Traditional Chinese Medicine of Jiangsu Province (No. HZ07097)
文摘Objective:To observe effects of Liandou Qingmai Recipe(连豆清脉方) on endothelin-1(ET-1),nitric oxide(NO),interleukin-6(IL-6) and IL-10 levels in patients with coronary heart disease.Methods:Total 101 cases with coronary heart disease were randomly divided into a treatment group(n=45) treated by Liandou Qingmai Recipe and a standard treatment group(control group,n=56),with a normal group of 16 health persons set up.Changes of ET-1,NO,IL-6 and IL-10 levels were measured before treatment and after treatment for two weeks.And the data were analyzed by SPSS 16.0 statistic software.Results:Before treatment,the levels of ET-1,IL-6 and IL-10 levels were significantly higher and NO was significantly lower in the patients with coronary heart disease than those in the normal group(90.7±12.7 ng/L vs 41.8±13.5 ng/L,9.17±0.18 ng/L vs 1.10±0.08 ng/L,1.94±0.26 ng/L vs 1.09±0.06 ng/L,and 92.2±17.7 μmol/L vs 124.5±27.2 μmol/L;all P<0.05),with no significant differences in the levels of ET-1,NO,IL-6 and IL-10 between the treatment group and the control group(P>0.05);After treatment,ET-1 and IL-6 significantly decreased in the treatment group and the control group,and NO increased in the treatment group;And IL-6 level was significantly lower and NO level was higher in the treatment group than those in the control group(4.48±1.22 ng/L vs 5.13±1.85 ng/L,117.4±22.3 μmol/L vs 92.4±17.1 μmol/L;both P<0.05);There was a positive correlation between IL-6 and IL-10,and a negative correlation between NO and IL-10(r=0.142,r=-0.152;both P<0.05).Conclusion:Liandou Qingmai Recipe can decline IL-6,IL-10 and ET-1 levels,and raise NO level in patients with coronary heart disease on the basis of standard treatment,so as to inhibit endothelial inflammatory response,improve vascular endothelial function,with stronger anti-AS action;And vascular endothelial lesion is related with inflammatory response.
文摘OBJECTIVE: To observe the influence of moxibustion temperature on blood lipids, endothelin-1(ET-1), nitric oxide(NO), and ET-1/NO in hyperlipidemia patients. METHODS: Forty-two primary hyperlipidemia patients were randomly divided into two groups of 21 and treated with moxibustion at different temperatures. Moxibustion was performed with the moxa roll 2.5-3.0 cm from the skin in the treatment group and 4 cm in the control group, 10 min per point, once every other day. Skin temperature was precisely measured with a thermometer during moxibustion. After a 12-week treatment, seven measurements of blood lipids, ET-1, and NO were recorded. RESULTS: Total cholesterol and triglyceride, were lower in the treatment group than in the control group(P0.05). Serum ET-1 and ET-1/NO was obvi-ously lowered in the treatment group(P0.001). Moxibustion regulated NO and ET-1/NO in the treatment group much better than in the control group. CONCLUSION: Moxibustion can regulate blood lipids and clear blood vessels. Moxibustion at 45℃has a better effect than moxibustion at 38℃ on regulating blood lipids and protecting vascular endothelial function, indicating that suitable temperature influences the curative effect of moxibustion.
文摘The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin?1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (PAPm) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FIO2 = 0.10) was 25 ?3.1 kPa and 68.7 ?10.2 kPa.s / L respectively. IG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of PAPm and PVR during hypoxic ventilation to 36.6 ?4.7 kPa and 158.4 ?25 kPa.s / L and its effect lasted for 2-3 hours. Meanwhile, plasma endothelin? level in the femoral artery increased by 20.9+ 7.1, 25.6?7.7, 28.6?7.9 pg / ml at the 60 th, 120th, 180th minute after the injection of L-NAME respectively (P<0.05 vs hypoxic control before the injection). In cultured endothelial cells from umbilical veins, endothelin-1 level of culture medium in control group was 35.1 ?.9 pg / 105 cells /ml (n=9). L-NAME increased endothelin-1 level to 42.8 ?4.9pg / 105 cells / ml (n = 9, P < 0.05) in case of 10-11 mol / L and to 43.0+ 4.7 pg / 105 cells / ml in case of 10 -7 mol/L (n=9, F<0.05). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin? in vivo and in cultured vascular endothelial cells.
文摘Background Nitric oxide (NO) plays an important role in acute lung injury (ALl), acute respiratory distress syndrome (ARDS), and in ventilator-induced lung injury (VILI). A change in the balance of endothelin-1 (ET-1) and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model. Methods Models of oleic acid induced ALl were established in dogs; these models were then randomized into three groups undergone different tidal volume (VT) mechanical ventilation, which included a VT6 group (VT equaled to 6 ml/kg body weight, positive end expiratory pressure (PEEP) equaled to 10 cmH20, n=-6), a VT10 group (VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH20, n=-4) and a VT20 group (VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH20, n=-6) for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial. Results PaO2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALl models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation (P 〈0.05) while the serum NO levels were similar in the three groups (all P 〉0.05). There was no significant difference in serum ratio of ET-1/NO between any two out of three groups (P 〉0.05), although there was a significant positive relationship between serum ET-1 and serum NO (r=0.80, P 〈0.01). The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group (both P 〈0.05) while there was no significant difference in lung NO levels between two groups (P〉0.05). In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation (P 〈0.05) as there was a significant positive relationship between ET-1 and NO in the lung (r=0.54, P 〈0.05). Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.
基金We are grateful to Betty Pace and Joann Moulds who graciously provided us with the genomic DNA samples.We acknowledge the assistance of Yi Li,Shanxi University,China with data analysis.This project was supported by a Research Laboratory Support and Faculty Development Award,College of Health Sciences and Technology,Rochester Institute of Technology(BNT).An ABRCMS Travel Award(KGN)to present this work at the Annual Biomedical Research Conference for Minority Students,Seattle WA November 12e15,2015 is acknowledged.
文摘Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals,the variability highlighted by differing genetic haplotypes.Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase(eNOS)and endothelin-1(ET-1)genes,the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear.To deconvolute their potential significance among African Americans with sickle cell disease,we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease(n Z 331)and control(n Z 379)groups,with a polymerase echain reaction restriction fragment length polymorphism assay.We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups.eNOS homozygote mutants,which had been shown to have clinical significance elsewhere,showed no statistical significance in our study.On the other hand,and contrary to previous report among Africans with sickle cell disease,the endothelin-1 homozygous mutant variant showed significant difference in genotypic(p Z 2.84E-12)and allelic frequencies(p Z 2.20E-16)between groups.The most common haplotype is the combination of T786C homozygote wildtype variant with homozygote mutant variants of G5665T(ET-1)and Glu298Asp(eNOS).These results show that endothelin-1(rs5370)polymorphism,rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease.This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications.
文摘AIM:To establish a rat ethanol gastritis model,we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis.METHODS:One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups:normal control group,undergoing gastric perfusion of normal saline(NS) by gastrogavage;model control group and 2 model therapy groups that underwent gastric perfusion with ethanol(distillate spirits with 56% ethanol content) by gastrogavage for 4 wk.Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups,while the same amount of NS,instead of geranylgeranylacetone was used in that model control group.The rats were then sacrificed and stomachs were removed.The injury level of the gastric mucosa was observed by light and electron microscopy,and the levels of prostaglandin 2(PGE 2),endothelin-1(ET-1) and nitric oxide(NO) were measured by radioimmunoassay and the Griess method.RESULTS:The gastric mucosal epidermal damage score(EDS;4.5) and ulcer index(UI;12.0) of the model control group were significantly higher than that of the normal control group(0 and 0 respectively,all P = 0.000).The gastric mucosal EDS and UI of the 2 model therapy groups(EDS:2.5 and 2.0;UI:3.5 and 3.0) were significantly lower than that of the model control group(all P < 0.01).There was no statistically significant difference between the low-dose and high-dose model therapy groups.The expression value of plasma ET-1 of the model control group was higher than that of the normal control group(P < 0.01) and the 2 model therapy groups(all P < 0.01).The expression values of gastric mucosal PGE 2 and serum NO of the model control group were lower than those of the normal control group(all P < 0.05) and the 2 model therapy groups(all P < 0.05).The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group(all P < 0.01) and the 2 model therapy groups(all P < 0.05).Scanning and transmission electron microscopy observation showed that in the model control group,the epithelial junctions were vague,the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group.However,in the 2 model therapy groups,damage to the intercellular joints and organelles was ameliorate relative to the model control group.CONCLUSION:Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion.The mechanism could be related to regulation of ET-1,NO and PGE 2.
基金this work was supported by Xi'an Science and technology Research Fund (GG04134)
文摘Objective To explore the correlation between endothelia cells activation and cytokines (ET-1, NO) levels in patients with pulmonary hypertension (PH), and to discuss their roles in the development of PH. Methods Twenty patients with simple ventricular septal defect (VSD) were chosen as controls, and 30 patients with PH were studied. Plasma levels of ET-1 and NO were measured by radioimmunoassay or colorimetric method. Before cardiopulmonary bypass was established, the specimens from right lung were fixed with formaldehyde solution, embedded with paraffin and stained by SP immunohistochemistry. Intercellular adhesion molecule-1 (ICAM-1) expression was measured through the determination of the light density with computer imaging technology. Results Compared with that of the patients with simple VSD, the light density of ICAM-1 and plasma level of ET-1 increased in patients with PH; but plasma level of NO decreased (P<0.05). Positive correlation was observed between ICAM-1 and ET-1/NO (P<0.05). Conclusion Endothelia cells activation and imbalance of ET-1/NO might play an important role in the development of PH.
基金We thank the support of National Nature Science Foundation of China(81771934)Shanghai Jiao Tong University Medical and Engineering Intersection Fund(YG2019ZDA03).
文摘Background:Reversibility of pulmonary hypertension(PH)is closely related to the treatment options for and prognosis of children with congenital heart disease.Objective:We combined patient-specific clinical features including diagnosis,age and echocardiographic results,and biomarkers of pulmonary vascular dysfunction to explore the noninvasive methods that can be used to accurately evaluate the reversibility of pulmonary hypertension in congenital heart disease(PH-CHD).Methods:Based on the preoperative systolic pulmonary arterial pressure(sPAP),70 CHD patients were divided into normal,PH-CHD suspected,and confirmed groups.Additionally,biomarkers of circulating endothelial cells(CECs),endothelin-1(ET-1),and endothelial nitric oxide synthase(eNOS)were detected.Patients were categorized into reversible(RPH)and irreversible(IRPH)groups according to the sPAP 6 months after surgery.Risk stratification was performed according to the clinical features and biomarkers.Results:CECs and ET-1 levels in the confirmed group were significantly higher.eNOS was higher in the confirmed and suspected groups than that in the normal group.CECs in the IRPH group were significantly higher compared to the RPH group.No such intergroup differences were observed with respect to ET-1 and eNOS levels.The ROC curve showed that the risk stratification was of high diagnostic value to evaluate reversibility.Conclusion:The CECs,eNOS,and ET-1 were closely related with PH-CHD.CECs and risk stratification have high practical value in assessing the reversibility of PH-CHD.
基金the National Natural Science Foundation of China, No. 3076031918
文摘For the treatment of brain ischemia using acupuncture, the needle is predominantly inserted into muscular layers and deep tissue. However, few studies have investigated the outcomes of shallow needling. The present study established middle cerebral artery occlusion models in rats using the thrombosis method. Shallow needling and conventional needling at the bilateral Neiguan (PC 6) and Gongsun (SP 4) acupoints improved neurological function of middle cerebral artery occlusion rats, increased the expression of the anti-apoptotic Bcl-2, inhibited the expression of the pro-apoptotic Bax, and reduced the expression of the vasoactive substances nitric oxide synthase and endothelin-1. However, these changes were more pronounced in the shallow needling group, indicating that shallow needling is more effective in inhibiting brain ischemic injury.
基金supported by Bureau of Traditional Chinese Medicine of Jiangsu Province(No.HZ07097)
文摘OBJECTIVE:To observe the effects of Liandouqingmai Recipe on life quality and vascular endothelial injury in patients with coronary heart disease.METHODS:Capitalized 101 patients with coronary heart disease were randomly divided into a treatment group(n=45) treated with Liandouqingmai Recipe and a standard treatment group(control group,n=56).A normal group of 16 healthy persons was additionally set up.Changes in ET-1 and NO levels were measured and Seatle Angina Questionnaire(SAQ) was adopted in studying life quality before and after treatment for two weeks.The data were analyzed with SPSS 16.0 statistic software.RESULTS:The average level of ET-1 in the normal group was lower and NO higher than that of patients with coronary heart disease.There was no significant difference in the average level of ET-1 and NO and in the scores of SAQ [physical limitation(PL),pngina stability(AS),apngina frequency(AF),treatment satisfaction(TS) and disease perception(DP)] between the two groups before treatment(P>0.05).But after treatment,the scores of SAQ(PL,AS,AF,TS,DP) and NO level were higher than those in the control group,and ET-1 average level in the treatment group was lower than that in the control group.The negative relations between PL and ET-1 and between AF and ET-1 were found in this study.CONCLUSION:Liandouqingmai Recipe can raise scores of SAQ and NO level and decline ET level in patients with coronary heart disease on the basis of convertional standard treatment,thus improving vascular endothelial function and life quality.Life quality is related to vascular endothelial function.