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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 investigate the effect of astragalus polysaccharide (APS) on rat myocardial fibrosis induced by isoproterenol (ISO) through transforming growth factor-β1 (TGF-β1) / Smads signaling pathway influences. Methods Sprague-Dawley (SD) rats were given APS 400 and 800 mg · kg -1, respectively. After 24 h, ip was administered with 10 mg · kg-1 ip for 14 days. The left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were recorded by a BL420 four-channel physiological recorder. The maximum systolic left ventricular pressure and maximum diastolic pressure heart rate index (HMI) and left ventricular mass index (LVMI); hematoxylin-eosin staining (hematoxylin-eosin staining) , HE staining and Sirius red staining. The morphology of myocardium was observed under light microscope and the collagen volume-integral (CVF) was measured. Western blotting was used to detect the expression of TGF-β1 and Smads protein. RT- β1 mRNA was detected by ELISA. The expression of propeptide of type I procollagen (PICP) and its inhibitor type I collagen carboxy-terminal cross-linked peptide (ICTP) content. Results Compared with normal group, cardiac function index of model group increased significantly (P <0.01), left ventricular mass index increased significantly (P <0.01), CVF increased significantly (P <0.01) / 3, Smad4 and TGF-β1 were significantly increased (P <0.01), the content of Smad 7 was significantly decreased (P <0.01), and the expression of TGF-β 1 mRNA was significantly increased (P <0.01). After administration of APS, cardiac function index decreased significantly (P <0.05), left ventricular mass index increased significantly (P <0.05), decreased CVF (P <0.05), Smad2 / 3 β1 protein content and mRNA expression were decreased (P <0.05), Smad7 protein content increased (P <0.05). PICP / ICTP could reflect the positive correlation with TGF-β 1 expression by ELISA, and the ratio was significantly decreased (P <0.05). Conclusion APS may play a role in the prevention and treatment of myocardial fibrosis induced by ISO. The mechanism is related to the inhibition of TGF-β 1 / Smads pathway.