摘要
目的:探讨转化生长因子β(TGF-β)/Smads信号通路与低氧高二氧化碳性肺动脉高压(HHPH)中肺动脉内皮-间充质转化(Endo MT)的关系及益气温阳活血化痰方的调控作用。方法:取健康雄性清洁级SD大鼠为研究对象,随机分为5组:常氧对照(N)组、低氧高二氧化碳(HH)组及益气温阳活血化痰方高剂量(YH)组、中剂量(YM)组和低剂量(YL)组。N组置于常氧环境下饲养,其余4组置于低氧高二氧化碳(9%~11%O2和5%~6%CO2)环境下饲养4周。各中药组在放入氧舱前以相同体积不同浓度的益气温阳活血化痰方灌胃,YH、YM和YL组浓度分别为200 g/L、100 g/L和50 g/L。术中测平均肺动脉压和平均颈动脉压,术毕取右心室游离壁及左心室加心室间隔称重,以此计算右心室肥大指数。HE染色和免疫荧光法观察肺组织形态学的变化,采用RT-PCR和Western blot检测α-平滑肌肌动蛋白(α-SMA)、CD31、TGF-β1和Smad2/3的m RNA和蛋白表达以及p-Smad2/3的蛋白水平。结果:与N组比,其余4组肺动脉平均压、α-SMA、TGF-β1和Smad2/3的m RNA和蛋白表达以及pSmad2/3的蛋白水平上升,CD31 m RNA和蛋白表达水平降低,镜下观察到组织形态学损伤;与HH组比,YH、YM和YL组肺动脉平均压、α-SMA、TGF-β1和Smad2/3的m RNA和蛋白表达以及p-Smad2/3的蛋白水平下降,CD31m RNA和蛋白表达水平上升,肺组织形态学的损伤显著减轻。结论:在HHPH中,TGF-β/Smads通路可能参与了Endo MT;益气温阳活血化痰方可通过抑制TGF-β/Smads通路的表达降低肺动脉高压。
AIM:To investigate the relationship between transforming growth factor-β(TGF-β)/Smads signaling pathway and pulmonary arterial endothelial-mesenchymal transition(EndoMT)in hypoxia-hypercapnia pulmonary hypertension(HHPH)process and the regulatory effect of Yiqi-Wenyang-Huoxue-Huatan formula(YWHHF).METHODS:Healthy male SD rats were randomly divided into5groups:normal control(N)group,hypoxia-hypercapnia(HH)group,high-dose YWHHF(YH)group,middle-dose YWHHF(YM)group and low-dose YWHHF(YL)group.The rats in N group was housed in normoxic environment,and the rats in the other4groups were housed in hypoxia-hypercapnia environment(9%~11%O2and5%~6%CO2)for4weeks,8h/d,6d/week.The excess water vapor was absorbed by anhydrous CaCl2,and CO2was absorbed by sodium hydroxide.The rats in YWHHF groups were put into the oxygen chamber before the same volume of YWHHF at different concentrations were given(200g/L for YH group,100g/L for YM group and50g/L for YL group).The average pulmonary artery pressure and the average carotid artery pressure were measured during the operation.After operation,the right ventricular free wall and left ventricle plus interventricular septum were collected for determining the right ventricular hypertrophy index.Moreover,the morphological changes of the lung tissues were observed under light microscope.The mRNA and protein levels ofα-smooth muscle actin(α-SMA),CD31,TGF-β1and Smad2/3,and the protein level of p-Smad2/3were detected by RT-PCR and Western blot.RESULTS:Compared with N group,the pulmonary artery mean pressure,the mRNA and protein expression ofα-SMA,TGF-β1and Smad2/3,and the protein level of p-Smad2/3were increased,the levels of CD31were decreased(P<0.05),and the lung tissue damage was observed in the other4groups.Compared with HH group,the pulmonary artery mean pressure,the mRNA and protein expression ofα-SMA,TGF-β1and Smad2/3,and the protein level of p-Smad2/3were decreased,while the mRNA and protein levels of CD31were increased.Moreover,the lung tissue damage was reduced in YH,YM and
作者
张聪聪
张晶晶
武垣伶
戴雍月
钱小英
王万铁
ZHANG Cong-cong;ZHANG Jing-jing;WU Yuan-ling;DAI Yong-yue;QIAN Xiao-ying;WANG Wan-tie(Department of Pathophysiology, Wenzhou Medical University, Wenzhou 325035, China;Department of Respiratory Medicine, Wenzhou People’s Hospital, Wenzhou 325000, China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第3期507-514,共8页
Chinese Journal of Pathophysiology
基金
浙江省中医药重点研究计划(No.2018ZZ018)
温州市高层次人才创新技术重点资助项目(No.2016-07)
