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
Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly reco...Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly recognised as a severe complication of HHT.PH may be categorised into two distinct types in patients with HHT.Post-capillary PH most often results from a high pulmonary blood flow that accompanies the high cardiac output state associated with liver arteriovenous malformations.Less frequently,the HHT-related gene mutations in ENG or ACVRL1 appear to predispose patients with HHT to develop pre-capillary pulmonary arterial hypertension.Differentiation between both forms of PH by right heart catheterisation is essential,since both entities are associated with severe morbidity and mortality with different treatment options.Therefore all HHT patients should be referred to an HHT centre.展开更多
Background Abnormal apoptosis of pulmonary artery smooth muscle cells （PASMCs） is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated pos...Background Abnormal apoptosis of pulmonary artery smooth muscle cells （PASMCs） is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated possible effect of endogenous hydrogen sulfide （H2S） on apoptosis of PASMCs during the development of pulmonary hypertension induced by high pulmonary blood flow. Methods Thirty-nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week shunt, 4-week shunt＋propargylglycine （PPG）, 11-week control, 11-week shunt and 11-week shunt＋sodium hydrosulfide （NariS） groups. Rats in 4-week shunt, 4-week shunt＋PPG, 11-week shunt and 11-week shunt＋NariS groups underwent an abdominal aorta-inferior vena cava shunt. Rats in 4-week shunt＋PPG group were intraperitoneally injected with PPG, an inhibitor of endogenous H2S production, for 4 weeks. Rats in 11-week shunt＋NariS group were intraperitoneally injected with NariS, a H2S donor, for 11 weeks. Lung tissue H2S was evaluated by sulfide-sensitive electrode. Apoptosis of PASMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling （TUNEL）. Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with immunochemical staining. Results Four weeks after the shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased （P 〈0.01）, but expression of bcl-2 increased significantly （P 〈0.01）. PPG administration further inhibited the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 （P 〈0.01）, but increased the expression of bcl-2 （P 〈0.01）. After 11 weeks of shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased （P 〈0.01）, but expression of bcl-2 increased obviously （P 〈0.01）. NariS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, but inhibited the expression of bcl-2. Conclusions H2S induces the apoptosis of PASMCs in the development of high pulmonary blood flow-induced pulmonary hypertension by activating the Fas pathway and inhibiting the bcl-2 pathway.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Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly recognised as a severe complication of HHT.PH may be categorised into two distinct types in patients with HHT.Post-capillary PH most often results from a high pulmonary blood flow that accompanies the high cardiac output state associated with liver arteriovenous malformations.Less frequently,the HHT-related gene mutations in ENG or ACVRL1 appear to predispose patients with HHT to develop pre-capillary pulmonary arterial hypertension.Differentiation between both forms of PH by right heart catheterisation is essential,since both entities are associated with severe morbidity and mortality with different treatment options.Therefore all HHT patients should be referred to an HHT centre.
基金This work was supported by grants from the Foundation of the Ministry of Education, China （No. 20070001702, 20070001770）, the National Natural Science Foundation of China （No. 30630031, 30821001, 30801251）, the Major Basic Research Development Program of China （No. 2006CB503807） and Beijing Natural Science Foundation （No. 7072082）.
文摘Background Abnormal apoptosis of pulmonary artery smooth muscle cells （PASMCs） is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated possible effect of endogenous hydrogen sulfide （H2S） on apoptosis of PASMCs during the development of pulmonary hypertension induced by high pulmonary blood flow. Methods Thirty-nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week shunt, 4-week shunt＋propargylglycine （PPG）, 11-week control, 11-week shunt and 11-week shunt＋sodium hydrosulfide （NariS） groups. Rats in 4-week shunt, 4-week shunt＋PPG, 11-week shunt and 11-week shunt＋NariS groups underwent an abdominal aorta-inferior vena cava shunt. Rats in 4-week shunt＋PPG group were intraperitoneally injected with PPG, an inhibitor of endogenous H2S production, for 4 weeks. Rats in 11-week shunt＋NariS group were intraperitoneally injected with NariS, a H2S donor, for 11 weeks. Lung tissue H2S was evaluated by sulfide-sensitive electrode. Apoptosis of PASMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling （TUNEL）. Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with immunochemical staining. Results Four weeks after the shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased （P 〈0.01）, but expression of bcl-2 increased significantly （P 〈0.01）. PPG administration further inhibited the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 （P 〈0.01）, but increased the expression of bcl-2 （P 〈0.01）. After 11 weeks of shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased （P 〈0.01）, but expression of bcl-2 increased obviously （P 〈0.01）. NariS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, but inhibited the expression of bcl-2. Conclusions H2S induces the apoptosis of PASMCs in the development of high pulmonary blood flow-induced pulmonary hypertension by activating the Fas pathway and inhibiting the bcl-2 pathway.
