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黄芪丹参水煎液抑制ISO诱导的大鼠心肌重构及其下调STIM1 TRPC1 CaN和NFATc3表达的机制(1)
http://www.100md.com 2017年10月8日 《中国中药杂志》 2017年第14期
     [摘要]探討黄芪丹参水煎液(HDD)对异丙肾上腺素(ISO)诱导大鼠心肌重构抑制作用和对STIM1,TRPC1,CaM,CaN,NFATc3表达的影响。 皮下注射 ISO(25 mg·kg-1·d-1,14 d)建立大鼠心肌重构模型,随机分为对照组、ISO模型组、HDD5(HDD 5 g·kg-1·d-1+ISO)组、HDD10(HDD 10 mg·kg-1·d-1+ISO)组。干预4周后,计算心脏质量指数(HW/BW)和左心室质量指数(LVW/BW);超声心动图观察心肌结构;HE染色观察心肌组织病理学结构变化;ELISA检测血清中 BNP,CaN和CaM kinases Ⅱ的水平;Western blot检测左心室组织 STIM1,TRPC1,pCaN,pNFATc3和NFATc3蛋白的表达。结果显示,ISO组大鼠HW/BW和LVW/BW均大于HDD5组和HDD10组(P<005);超声心动图检查结果显示,HDD能够抑制 ISO诱导的LVEDD,LVESD增加;ELISA检测显示,HDD能明显抑制ISO致心肌重构大鼠血清中BNP,CaN和CaM kinases Ⅱ含量的升高(P<001)。Western blot 检测结果显示,ISO组大鼠心肌组织STIM1,TRPC1,pCaN,pNFATc3和NFATc3表达升高,HDD给药后心肌组织内STIM1,TRPC1,pCaN,pNFATc3和NFATc3的表达均降低(P<005)。 结果表明,黄芪丹参水煎液具有抑制ISO致大鼠心肌重构的作用,其机制与下调STIM1,TRPC1,CaM kinases Ⅱ,pCaN/CaN和pNFATc3/NFATc3表达有关。
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    [关键词]黄芪丹参水煎液; 心肌重构; 基质相互作用分子1; 瞬时受体电位通道1

    [Abstract]To investigate the inhibitory effect of Huangqi Danshen decoction (HDD) on isoproterenol (ISO)induced myocardial remodeling and explore its effect on STIM1, TRPC1, CaN and NFATc3 expressions ISO (25 mg·kg-1·d-1×14 d) was given by subcutaneous injection to establish myocardial remodeling models in rats, and then were randomly divided into control group, ISO model group, HDD5 group (HDD 5 g·kg-1·d-1+ISO), and HDD10 group (HDD 10 g·kg-1·d-1+ISO) After intervention for 4 weeks, the heart mass index (HW/BW) and the left ventricular mass index (LVW/BW) were calculated; the structure of myocardium was observed by echocardiography; the pathological changes of myocardium were observed by HE staining; levels of BNP, CaN and CaM kinases II in serum were detected by ELISA, and the protein expression levels of STIM1, TRPC1, pCaN, pNFATc3, and NFATc3 in left ventricular tissues were detected by Western blot The results showed that the HW/BW and LVW/BW in ISO group were greater than those in HDD5 group and HDD10 group (P<005); Echocardiography showed that HDD inhibited ISOinduced increase in LVEDD and LVESD; ELISA results showed that HDD could significantly inhibit the increase of BNP, CaN and CaM kinases II levels in serum of rats with ISOinduced myocardial remodeling (P<001) Western blot results showed that STIM1, TRPC1, pCaN, pNFATc3 and NFATc3 expression levels were increased in the myocardial tissues of ISO group rats, and after HDD administration, the above expression levels were decreased in group ISO, HDD for myocardial tissue after administration of STIM1, TRPC1, pCaN, pNFATc3 and NFATc3 expression decreased (P<005) Our findings indicated that HDD can attenuate the myocardial remodeling induced by ISO, and its mechanism may be related to downregulating the expression levels of STIM1, TRPC1, CaM kinases II, pCaN/CaN and pNFATc3/NFATc3, 百拇医药(王新东 祁晓霞 卞勇 陈晓栋 张一炎 方祝元)
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