蛇床子素通过上调eNOS/PKG-1通路抗野百合碱所致大鼠肺动脉高压  

Osthole inhibits monocrotaline-induced pulmonary arterial hypertension in rats via up-regulating eNOS/PKG-1 pathway

作　　者：任星桥 李晓彤 林小英 曾凡群 李叶丽 杨丹莉 Ren Xingqiao;Li Xiaotong;Lin Xiaoying;Zeng Fanqun;Li Yeli;Yang Danli(Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi City,Guizhou 563099,China;School of Pharmacy,Zunyi Medical University,Zunyi City,Guizhou 563099,China)

机构地区：[1]遵义医科大学基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室 [2]遵义医科大学药学院,贵州遵义563099

出　　处：《遵义医科大学学报》2021年第5期614-618,624,共6页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:81860647)。

摘　　要：目的借助工具药N^(G)-硝基左旋精氨酸甲酯(L-NAME),探讨内皮型一氧化氮合酶(eNOS)/蛋白激酶G1(PKG-1)通路在蛇床子素(Ost)干预野百合碱(MCT)所致大鼠肺动脉高压(PAH)中的作用。方法在60只雄性Sprague-Dawley(SD)大鼠中随机抽取10只为正常对照组(Control组)。除Control组外,其余大鼠均采用颈背部一次性皮下注射MCT(55 mg/kg),建立PAH模型,并随机分为模型组(MCT组)、蛇床子素组(Ost组)、Ost+L-NAME组、L-精氨酸组(L-arg组)、L-arg+L-NAME组,后四组在建模第14天至第28天分别给予相应药物干预(qd)。在造模第28天,采用右心导管术检测大鼠肺动脉平均压(mPAP);称大鼠体重和肺组织重量,计算肺重指数(LI);H&E染色观察肺小动脉的形态学变化;蛋白免疫印迹法检测肺组织eNOS和PKG-1蛋白的表达。结果与Control组相比,MCT组大鼠肺动脉平均压和肺重指数均明显升高(P<0.05);肺小动脉血管壁增厚、管腔明显狭窄;肺组织eNOS与PKG-1蛋白表达均显著下调(P<0.05)。与MCT组相比,Ost组和L-arg组大鼠肺动脉平均压和肺重指数均明显下降(P<0.05);肺小动脉血管壁增厚、管腔狭窄的变化有所改善;肺组织eNOS与PKG-1蛋白表达均明显上调(P<0.05)。而给予L-NAME能明显拮抗Ost和L-arg的上述作用(P<0.05)。结论Ost改善野百合碱所致大鼠PAH的机制至少与上调eNOS/PKG-1通路有关。Objective To investigate the role of eNOS/PKG-1 pathway in Osthole(Ost)intervention in pulmonary arterial hypertension induced by monocrotaline(MCT)in Sprague Dawley(SD)rats with the aid of the tool medicine,NOS inhibitor,L-NAME.Methods Sprague-Dawley(SD)rats(male,n=10)were randomly selected as the normal control group(control).Except for the control group,the other rats were injected with MCT(55 mg/kg)subcutaneously to establish PAH model.After 14 days,all the PAH rats were randomly divided into five groups,which were MCT group(MCT),Osthole group(Ost),Osthole+NOS inhibitor group(Ost+L-NAME),L-arginine group(L-arg),L-arginine+NOS inhibitor group(L-arg+L-NAME).After 14th days of modeling,the MCT group was given the equal volume of saline;while the rats in other groups were intervened with the above medicines respectively for 14 days for once a day.On 28th days of modeling,mean pulmonary artery pressure(mPAP)was detected by right heart catheterization;Body weight and lung weight were weighed and lung weight index(LI)was calculated;Morphology of the small pulmonary artery was observed by H&E;Protein expression of eNOS and PKG-1 in lung tissue was detected by Western blot.Results Compared with control group,mPAP and LI in MCT group were increased significantly(P<0.05);H&E staining showed that the pulmonary artery wall was thickened and the luminal stenosis was evident;the expression of eNOS and PKG-1 in lung tissue was significantly down-regulated(P<0.05).After administration of Ost and L-arg,mPAP and LI were decreased significantly(P<0.05);H&E staining showed that the pulmonary artery wall thickening and lumen stenosis were improved;the protein expression of eNOS and PKG-1 in lung tissue was significantly up-regulated(P<0.05).However,L-NAME treatment could inhibit the above effects of Ost and L-arg.Conclusion Osthole inhibits the monocrotaline-induced pulmonary arterial hypertension in rats,and the mechanism may be at least via up-regulating eNOS/PKG-1 pathway.

关 键 词：蛇床子素 野百合碱 肺动脉高压 内皮型一氧化氮合酶 蛋白激酶G1 

分 类 号：R285.5[医药卫生—中药学]