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
The expression of endothelial nitric oxide synthase traffic inducer （NOSTRIN） in the placenta of the patients with pregnancy induced hypertension （PIH） was detected and its role in the pathogenesis of PIH was stud...The expression of endothelial nitric oxide synthase traffic inducer （NOSTRIN） in the placenta of the patients with pregnancy induced hypertension （PIH） was detected and its role in the pathogenesis of PIH was studied. The pathological changes in placental vessels were observed by HE staining. NO2-/NO3- , the stable metabolic end products of NO, was measured with nitrate reductase. The eNOS activity in placental tissues was assayed by spectrophotometry. Western blot analysis was applied to detect NOSTRIN expression. The incidence of thickening and fibronoid necrosis of placental vessels was significantly higher in women with PIH than in the normal group （P〈 0.01）. The levels of placental NO2-/NO3- in PIH patients （27. 53±7.48 μmol/mg） were significantly lower than in normal group （54. 27±9.53 μmol/mg, P〈0.01）. The activity of eNOS was significantly decreased in PIH group （12. 826±3.61 U/mg） as compared with that in normal group （21. 72±3.83 U/mg, P〈0.01）. Western blot analysis revealed that both groups expressed 58 kD NOSTRIN, but the protein level was significantly higher in women with PIH than in the normal group （P〈0.01）. A significant negative correlation existed between the expression of NOSTRIN protein and the activity of eNOS in placental tissue of women with PIH （r=-0.57, P〈0.01）. It was concluded that the level of NOSTRIN expression in placenta of women with PIH was increased, which may play an important role in the pathogenesis of PIH.展开更多
Objective: To explore the role of nitric oxide (NO), an internal vasodilative factor, in occurrence ofpregnancy induced hypertension (PIH). Methods: The antepartum and postpartum levels of NO2-/NO3-, the stable metabo...Objective: To explore the role of nitric oxide (NO), an internal vasodilative factor, in occurrence ofpregnancy induced hypertension (PIH). Methods: The antepartum and postpartum levels of NO2-/NO3-, the stable metabolic end product of NO, and those of cyclic guanosine monophosphate (cGMP) in 30 patients with PIHand 30 healthy women in their late pregnancy were measured with greiss reagent. ResultS: ① The plasma levels ofNO2-/NO3- and cGMP were significantly decreased in patients with PIH as compared with the healthy women (P<0. 05). ②In patients with PlH, the antepartum level of NO2-/NO3- was markedly lower than the postpartum one(P<O. ol ). ③There was a negative correlation between the level of plasma NO2- /NO3- and systolic blood pressurein patients with PIH (P<0. 01). ④ A positive correlation was found between the level of plasma NO2-/NO3- andthat of cGMP in patients with PIH (P<0. 01). Conclusion: The decrease of NO synthesis may play an importantrole in occurrence of PIH.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
Expression of endogenous ouabain in placenta and the concentrations of serum ET-1 and NO were examined in 30 patients with hypertensive disorder complicating pregnancy （HDCP） and 30 healthy pregnant women to investi...Expression of endogenous ouabain in placenta and the concentrations of serum ET-1 and NO were examined in 30 patients with hypertensive disorder complicating pregnancy （HDCP） and 30 healthy pregnant women to investigate the effect of endogenous ouabain on HDCP. Compared with the healthy pregnant group, the expression of endogenous ouabain dramatically increased in the HDCP groups （P〈0.01）. There was a significantly positive correlation between the expression of en- dogenous ouabain with ET-1 （r= 0.5567, P〈0.01）, while the correlation of endogenous ouabain and NO was significantly negative （r=-0.6895, P〈0.01）. As expected, the correlation between ET-1 and NO was negative （r=-0.7796, P〈0.01）. ET-1 concentrations of maternal and cord sera in HDCP groups were significantly higher in comparison with healthy pregnant group （P〈0.01）. On the contrast, NO concentrations were much lower in the maternal and cord sera of HDCP groups as compared with healthy pregnant group （P〈0.01）. Our data suggest that endogenous ouabain is directly involved in the nosogenesis of HDCP, with accompanying decreased NO and the elevated of ET-1.展开更多
Objective: To study the effect of low molecular weight heparin therapy on maternal endothelial injury and placental pathological injury after hypertensive disorder complicating pregnancy. Methods: A total of 70 patien...Objective: To study the effect of low molecular weight heparin therapy on maternal endothelial injury and placental pathological injury after hypertensive disorder complicating pregnancy. Methods: A total of 70 patients with hypertensive disorder complicating pregnancy who were treated in the hospital between September 2014 and May 2016 were divided into control group and observation group according to the random number table method, 35 cases in each group. Control group received conventional therapy, the observation group received low molecular weight heparin combined with conventional therapy, and both therapies lasted until delivery. The differences in the levels of endothelial injury indexes in serum as well as the expression of oxidative stress indexes and apoptosis molecules in the placental grinding fluid were compared between the two groups of patients. Results: After treatment, serum ET and VCAM-1 levels of both groups of patients were lower than those before treatment while NO and PGE levels were higher than those before treatment, and serum ET and VCAM-1 levels of observation group were lower than those of control group while NO and PGE levels were higher than those of control group;after delivery, AOPP and MDA levels in placental grinding fluid were significantly lower than those of control group while SOD and GSH-Px levels were higher than those of control group;Fas, p53 and caspase-3 mRNA expression in placental grinding fluid were lower than those of control group while Bcl-2 and bax mRNA expression were higher than those of control group. Conclusion: Adjuvant low molecular weight heparin therapy can help to reduce the maternal endothelial injury, reduce the systemic oxidative stress and suppress the placental cell apoptosis in patients with hypertensive disorder complicating pregnancy.展开更多
Background This is a prospective clinical study based on a large sample gathered from multiple centers in China, subordinating to 10th Five-Year Plan of National Science ＆ Technology Progression. We analyzed the high...Background This is a prospective clinical study based on a large sample gathered from multiple centers in China, subordinating to 10th Five-Year Plan of National Science ＆ Technology Progression. We analyzed the high-risk factors inducing hypertensive disorders in pregnancy （HDP） and estimated the potential effect of anti-oxidants administration, including vitamin C （VC）, vitamin E （VE） and Salvia Miltiorrhiza L （SML）, a Chinese herb medicine, in amelioration of the high-risk factors in pregnancy. Methods From April 2005 to July 2006, 4814 pregnant women from 24 national wide cooperative hospitals were involved in this prospective research. The participants were randomly divided into two groups： 1607 cases were in anti-oxidants group with administration of vitamins and SML; 3207 cases were in control group without any medicine given. Every participant was under monitoring for the morbidity of HDP and the high-risk factors were investigated in HDP cases in each group. Results （1）The morbidity of HDP was 3.55% in anti-oxidants group vs. 4.18% in control group. No statistical difference existed between the two groups （P〉0.05）. （2） In anti-oxidants group, the HDP morbidities among three subgroups： VC ＋ VE ＋ SML, VC ＋ VE and SML only, were 5.51%, 3.05% and 5% respectively. It showed no statistical difference among three remedies （P 〉0.05）. （3） The related index of factors affecting HDP showed in intensity sequence as follows： family HDP history 〉 profession 〉 education level 〉 age 〉 body weight. The incidence of HDP in normal population was 3.51%, and the incidence of HDP in high-risk pregnant women （family HDP history, heavy physical labor, low education level （middle school and below）, age 〉40, body mass index 〉24） was 5.84%, which was obviously higher than that in normal population （P 〈0.01）. In anti-oxidants group, the probability of HDP in women with high-risk factors was 3.81%, which was obviously lower than that in control group with high-risk factors at 7.14% （P〈0.01）. （4） In control group, the morbidity of HDP in women with family HDP history （especially with sisters＇）, heavy physical labor, middle school and below, age 〉35 was： 50.00%, 15.22%, 6.33%, 26.28% and 5.75%, respectively, and that in anti-oxidants group was 0, 7.69%, 3.74%, 9.27% and 2.67%, respectively, which was obviously lower than that in control group. Conclusions The high-risk factors prone to induce HDP included： family history of HDP, heavy physical labor, low education level, aging and obesity. No impressive effect of anti-oxidants application was found in preventing HDP in general population but the remedy demonstrated positive effect on preventing HDP in pregnant women with high-risk factors.展开更多
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The expression of endothelial nitric oxide synthase traffic inducer （NOSTRIN） in the placenta of the patients with pregnancy induced hypertension （PIH） was detected and its role in the pathogenesis of PIH was studied. The pathological changes in placental vessels were observed by HE staining. NO2-/NO3- , the stable metabolic end products of NO, was measured with nitrate reductase. The eNOS activity in placental tissues was assayed by spectrophotometry. Western blot analysis was applied to detect NOSTRIN expression. The incidence of thickening and fibronoid necrosis of placental vessels was significantly higher in women with PIH than in the normal group （P〈 0.01）. The levels of placental NO2-/NO3- in PIH patients （27. 53±7.48 μmol/mg） were significantly lower than in normal group （54. 27±9.53 μmol/mg, P〈0.01）. The activity of eNOS was significantly decreased in PIH group （12. 826±3.61 U/mg） as compared with that in normal group （21. 72±3.83 U/mg, P〈0.01）. Western blot analysis revealed that both groups expressed 58 kD NOSTRIN, but the protein level was significantly higher in women with PIH than in the normal group （P〈0.01）. A significant negative correlation existed between the expression of NOSTRIN protein and the activity of eNOS in placental tissue of women with PIH （r=-0.57, P〈0.01）. It was concluded that the level of NOSTRIN expression in placenta of women with PIH was increased, which may play an important role in the pathogenesis of PIH.
文摘Objective: To explore the role of nitric oxide (NO), an internal vasodilative factor, in occurrence ofpregnancy induced hypertension (PIH). Methods: The antepartum and postpartum levels of NO2-/NO3-, the stable metabolic end product of NO, and those of cyclic guanosine monophosphate (cGMP) in 30 patients with PIHand 30 healthy women in their late pregnancy were measured with greiss reagent. ResultS: ① The plasma levels ofNO2-/NO3- and cGMP were significantly decreased in patients with PIH as compared with the healthy women (P<0. 05). ②In patients with PlH, the antepartum level of NO2-/NO3- was markedly lower than the postpartum one(P<O. ol ). ③There was a negative correlation between the level of plasma NO2- /NO3- and systolic blood pressurein patients with PIH (P<0. 01). ④ A positive correlation was found between the level of plasma NO2-/NO3- andthat of cGMP in patients with PIH (P<0. 01). Conclusion: The decrease of NO synthesis may play an importantrole in occurrence of PIH.
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 Scientific Research Foundation for the Returned Overseas ChineseScholars, State Education Ministry (NO:200414519001).
文摘Expression of endogenous ouabain in placenta and the concentrations of serum ET-1 and NO were examined in 30 patients with hypertensive disorder complicating pregnancy （HDCP） and 30 healthy pregnant women to investigate the effect of endogenous ouabain on HDCP. Compared with the healthy pregnant group, the expression of endogenous ouabain dramatically increased in the HDCP groups （P〈0.01）. There was a significantly positive correlation between the expression of en- dogenous ouabain with ET-1 （r= 0.5567, P〈0.01）, while the correlation of endogenous ouabain and NO was significantly negative （r=-0.6895, P〈0.01）. As expected, the correlation between ET-1 and NO was negative （r=-0.7796, P〈0.01）. ET-1 concentrations of maternal and cord sera in HDCP groups were significantly higher in comparison with healthy pregnant group （P〈0.01）. On the contrast, NO concentrations were much lower in the maternal and cord sera of HDCP groups as compared with healthy pregnant group （P〈0.01）. Our data suggest that endogenous ouabain is directly involved in the nosogenesis of HDCP, with accompanying decreased NO and the elevated of ET-1.
文摘Objective: To study the effect of low molecular weight heparin therapy on maternal endothelial injury and placental pathological injury after hypertensive disorder complicating pregnancy. Methods: A total of 70 patients with hypertensive disorder complicating pregnancy who were treated in the hospital between September 2014 and May 2016 were divided into control group and observation group according to the random number table method, 35 cases in each group. Control group received conventional therapy, the observation group received low molecular weight heparin combined with conventional therapy, and both therapies lasted until delivery. The differences in the levels of endothelial injury indexes in serum as well as the expression of oxidative stress indexes and apoptosis molecules in the placental grinding fluid were compared between the two groups of patients. Results: After treatment, serum ET and VCAM-1 levels of both groups of patients were lower than those before treatment while NO and PGE levels were higher than those before treatment, and serum ET and VCAM-1 levels of observation group were lower than those of control group while NO and PGE levels were higher than those of control group;after delivery, AOPP and MDA levels in placental grinding fluid were significantly lower than those of control group while SOD and GSH-Px levels were higher than those of control group;Fas, p53 and caspase-3 mRNA expression in placental grinding fluid were lower than those of control group while Bcl-2 and bax mRNA expression were higher than those of control group. Conclusion: Adjuvant low molecular weight heparin therapy can help to reduce the maternal endothelial injury, reduce the systemic oxidative stress and suppress the placental cell apoptosis in patients with hypertensive disorder complicating pregnancy.
文摘Background This is a prospective clinical study based on a large sample gathered from multiple centers in China, subordinating to 10th Five-Year Plan of National Science ＆ Technology Progression. We analyzed the high-risk factors inducing hypertensive disorders in pregnancy （HDP） and estimated the potential effect of anti-oxidants administration, including vitamin C （VC）, vitamin E （VE） and Salvia Miltiorrhiza L （SML）, a Chinese herb medicine, in amelioration of the high-risk factors in pregnancy. Methods From April 2005 to July 2006, 4814 pregnant women from 24 national wide cooperative hospitals were involved in this prospective research. The participants were randomly divided into two groups： 1607 cases were in anti-oxidants group with administration of vitamins and SML; 3207 cases were in control group without any medicine given. Every participant was under monitoring for the morbidity of HDP and the high-risk factors were investigated in HDP cases in each group. Results （1）The morbidity of HDP was 3.55% in anti-oxidants group vs. 4.18% in control group. No statistical difference existed between the two groups （P〉0.05）. （2） In anti-oxidants group, the HDP morbidities among three subgroups： VC ＋ VE ＋ SML, VC ＋ VE and SML only, were 5.51%, 3.05% and 5% respectively. It showed no statistical difference among three remedies （P 〉0.05）. （3） The related index of factors affecting HDP showed in intensity sequence as follows： family HDP history 〉 profession 〉 education level 〉 age 〉 body weight. The incidence of HDP in normal population was 3.51%, and the incidence of HDP in high-risk pregnant women （family HDP history, heavy physical labor, low education level （middle school and below）, age 〉40, body mass index 〉24） was 5.84%, which was obviously higher than that in normal population （P 〈0.01）. In anti-oxidants group, the probability of HDP in women with high-risk factors was 3.81%, which was obviously lower than that in control group with high-risk factors at 7.14% （P〈0.01）. （4） In control group, the morbidity of HDP in women with family HDP history （especially with sisters＇）, heavy physical labor, middle school and below, age 〉35 was： 50.00%, 15.22%, 6.33%, 26.28% and 5.75%, respectively, and that in anti-oxidants group was 0, 7.69%, 3.74%, 9.27% and 2.67%, respectively, which was obviously lower than that in control group. Conclusions The high-risk factors prone to induce HDP included： family history of HDP, heavy physical labor, low education level, aging and obesity. No impressive effect of anti-oxidants application was found in preventing HDP in general population but the remedy demonstrated positive effect on preventing HDP in pregnant women with high-risk factors.
