作　　者： (朱晓雨）; (王洪新）; (李佳莘）; (杜艳青）; (朱英伟）;

机构地区： 锦州医科大学心脑血管药物研究重点实验室,辽宁锦州121001

出　　处： 《沈阳药科大学学报》 2017年第8期686-693,共8页

摘　　要： 目的观察黄芪多糖(astragalus polysaccharide,APS)通过转化生长因子-β1(transforming growth Factor-β1,TGF-β1)/Smads信号传导通路对异丙肾上腺素(isoproterenol,ISO)诱导的大鼠心肌纤维化的影响。方法 SD(Sprague-Dawley)大鼠分别ig给予APS 400和800 mg·kg^(-1),24 h后ip给予ISO 10 mg·kg-1,连续14 d。BL420型四道生理记录仪记录左心室收缩最大压(left ventricular systolic pressure,LVSP)及左心室舒张末压(left ventricular end-diastolic pressure,LVEDP),左心室最大收缩、舒张期压力微分(maximum rate of rise/decrease of LVSP,±dp/dtmax)全心质量指数(heart mass index,HMI)和左心室质量指数(left ventricular mass index,LVMI);苏木精-伊红染色法(hematoxylin-eosin staining,HE)染色和天狼星红染色,在光镜下观察其心肌形态并测定其胶原容积积分(collagenvol-umefraction,CVF);Western蛋白印迹法测定TGF-β1和Smads蛋白的表达;RT-PCR测定TGF-β1mRNA的表达;ELISA测定I型前胶原羧基前肽(propeptide of type I procollagen,PICP)及其抑制物I型胶原交联羧基末端肽(type I collagen carboxy-terminal cross-linked peptide,ICTP)的含量。结果与正常组相比,模型组大鼠心功能指数显著上升(P<0.01);左心室质量指数显著上升(P<0.01);CVF显著上升(P<0.01);PICP/ICTP明显上升,Smad2/3,Smad4及TGF-β1的蛋白含量显著上升(P<0.01);Smad 7蛋白含量显著下降(P<0.01);TGF-β_1 mRNA的表达明显升高(P<0.01)。给药APS后,心功能指数可明显下降(P<0.05),左心室质量指数显著上升(P<0.05),CVF减少(P<0.05),Smad2/3(P<0.05),Smad4及TGF-β1的蛋白含量及mRNA的表达均下降(P<0.05),Smad7的蛋白含量上升(P<0.05)。通过ELISA测定PICP/ICTP能反映与TGF-β_1表达呈正相关性,其比值明显下降(P<0.05)。结论 APS对ISO诱导的心肌纤维化有一定的防治作用,其机制与抑制TGF-β_1/Smads通路相关。 Objective To explore the mechanism of astragalus polysaccharide （APS）on the myocardial fibrosis induced by isoproterenol （ISO）though TGF-β1/Smads pathway in rats. Methods ISO 5 mg. kg-1, ip, 14 d for myocardial fibrosis in the rats model. Forty SD rats were randomly divided into six groups： normal control, model, ISO ＋ APS400 mg- kg - 1 , ISO ＋ 800 mg. kg - 1. 400 and 800 mg. kg - 1 were gavage before given ISO 5 mg. kg - 1, ip, rats were given for 4 w. Heart mass index and left ventricular mass index of rats in each group were calculated, and the cardiac function was tested. The degree of myocardial fibrosis was observed with hematoxylin-eosin staining （HE） staining and Sirius red staining method. The collagen volume fraction（CVF） in left ventricular was measured after Sirius red staining. The expressions of TGF-β1 and Smads in the tissue were measured by Western blot. The mRNA expression level of TGF-β1 was measured by RT-PCR. ELISA was used to detect the contents of carboxy-terminal propeptide of type I procollagen （PICP）and type I collagen carboxy-terminal cross-linked peptide （ICTP）in serum. Results APS was significantly inhibited by myocardial fibrosis. Compared to the isoproterenol group ,400,800 mg. kg-1 propranolol decreased HMI and LVMI, and CVF, and could significantly down-regulated the overexpression of TGF-β1 mRNA, and decreased the expression of TGF-β1, Smad2/3, Smad4, and increased the expression of Smad7. The radio was decreased reflected a positive correlation between PICP / ICTP and TGF-β1. APS can significantly reduce the degree of myocardial fibrosis in rats. Compared with the ISO group, cardiac functional index,left ventricular and CVF mass index were decreased, decreased the expression of TGF-β1, Smad2/3, Smad4, and increased the expression of Smad7. The result were decreased showed positively correlate with PICP/ICTP and expression of TGF-β1. Conclusions Astragalus polysaccharide has a protective effect on isoproterenol-induced myocardial fibrosis, wh

关 键 词： 黄芪多糖 异丙肾上腺素 心肌纤维化 蛋白