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
Objective To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension(PAH) in patients of chronic obstructive pulmonary disease(COPD) associated with chronic cor pulmonale(C...Objective To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension(PAH) in patients of chronic obstructive pulmonary disease(COPD) associated with chronic cor pulmonale(CCP) during exacerbation.Methods Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group.The control group received standard treatment with antibiotics,antiasthmatic and expectorant medications,and oxygenation;and the ligustrazine treatment group received ligustrazine treatment(80 mg/d;i.v.;for 2 weeks) in addition to the standard treatment.Before and at the end of 2 week treatment,the clinic responses of the two regimens were evaluated,plasma levels of endothelin-1(ET-1) and nitric oxide(NO) were determined;arterial oxygen partial pressure(PaO_2),mean pulmonary arterial pressure(mPAP),outflow tract of right ventricle(RVOT),and internal diameter of right ventricle(RV) were measured.Results Good clinic benefits were achieved in both the standard and ligustrazine regimens,plasma level of ET-1,values of mPAP,RV and RVOT decreased significantly,plasma level of NO and PaO_2 values decreased(all P<0.01 vs pretreatment to all parameters).Compared with the control group,ligustrazine greatly enhanced the clinic efficacy from 77.1%to 97.1%(P<0.05),and also resulted in more significant changes of all these parameters(P<0.01 vs control group for all parameters).For both groups,the levels of plasma ET-1 were positively correlated with values of mPAP,RVOT,and RV(r = 0.710,0.853,and 0.766,respectively,all P = 0.000),and negatively correlated with plasma NO and PaO_2(r =- 0.823,and- 0.752,respectively,all P = 0.000).Conclusion Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area.The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells,thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.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
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
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
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
A microwave-assisted solid phase synthesis for endothelin 1 is presented.Reduced endothelin 1 was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.The who...A microwave-assisted solid phase synthesis for endothelin 1 is presented.Reduced endothelin 1 was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.The whole peptide was cleaved from the resin and two disulphide bridges were formed under air oxidation at room temperature.The purity and efficiency of synthesizing the peptide is much higher than other methods used before.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
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
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.
基金supported by the Key scientific and technological project in Qinghai Province,China (2006-N-143)
文摘Objective To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension(PAH) in patients of chronic obstructive pulmonary disease(COPD) associated with chronic cor pulmonale(CCP) during exacerbation.Methods Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group.The control group received standard treatment with antibiotics,antiasthmatic and expectorant medications,and oxygenation;and the ligustrazine treatment group received ligustrazine treatment(80 mg/d;i.v.;for 2 weeks) in addition to the standard treatment.Before and at the end of 2 week treatment,the clinic responses of the two regimens were evaluated,plasma levels of endothelin-1(ET-1) and nitric oxide(NO) were determined;arterial oxygen partial pressure(PaO_2),mean pulmonary arterial pressure(mPAP),outflow tract of right ventricle(RVOT),and internal diameter of right ventricle(RV) were measured.Results Good clinic benefits were achieved in both the standard and ligustrazine regimens,plasma level of ET-1,values of mPAP,RV and RVOT decreased significantly,plasma level of NO and PaO_2 values decreased(all P<0.01 vs pretreatment to all parameters).Compared with the control group,ligustrazine greatly enhanced the clinic efficacy from 77.1%to 97.1%(P<0.05),and also resulted in more significant changes of all these parameters(P<0.01 vs control group for all parameters).For both groups,the levels of plasma ET-1 were positively correlated with values of mPAP,RVOT,and RV(r = 0.710,0.853,and 0.766,respectively,all P = 0.000),and negatively correlated with plasma NO and PaO_2(r =- 0.823,and- 0.752,respectively,all P = 0.000).Conclusion Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area.The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells,thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.
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 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 key project of Chinese Ministry of Education(No.109086)
文摘A microwave-assisted solid phase synthesis for endothelin 1 is presented.Reduced endothelin 1 was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.The whole peptide was cleaved from the resin and two disulphide bridges were formed under air oxidation at room temperature.The purity and efficiency of synthesizing the peptide is much higher than other methods used before.
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.
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.
