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  

Huangqi Danshen decoction attenuates isoproterenol-induced myocardial remodeling via STIM1,TRPC1,CaN and NFATc3 pathways in rats

作　　者：王新东[1,2] 祁晓霞[1] 卞勇[1] 陈晓栋[2] 张一炎[2] 方祝元[1] WANG Xin-dong QI Xiao-xia BIAN Yong CHEN Xiao-dong ZHANG Yi-yan FANG Zhu-yuan(The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210026, China Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China)

机构地区：[1]南京中医药大学第一临床学院,江苏南京210026 [2]江苏省中医药研究院,江苏南京210028

出　　处：《中国中药杂志》2017年第14期2738-2743,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金青年基金项目(81403386);江苏省自然科学基金青年基金项目(BK20161078);中国中医科学院江苏分院课题(JSBY1316)

摘　　要：探讨黄芪丹参水煎液(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,Ca M,Ca N,NFATc3表达的影响。皮下注射ISO(2.5 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,Ca N和Ca M kinasesⅡ的水平;Western blot检测左心室组织STIM1,TRPC1,p-Ca N,p-NFATc3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<0.05);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,Ca N和Ca M kinasesⅡ含量的升高(P<0.01)。Western blot检测结果显示,ISO组大鼠心肌组织STIM1,TRPC1,p-Ca N,p-NFATc3和NFATc3表达升高,HDD给药后心肌组织内STIM1,TRPC1,p-Ca N,p-NFATc3和NFATc3的表达均降低(P<0.05)。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,Ca M kinasesⅡ,p-Ca N/Ca N和pNFATc3/NFATc3表达有关。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 （2.5 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 mod- el group, HDDs 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 myocardiumwas 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, p-CaN, p-NFATc3, 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 〈 0. 05 ） ; Echocardiography showed that HDD inhibited ISO-induced in- crease 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 ISO-induced myocardial remodeling （P 〈 0. 01 ）. Western blot results showed that STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression levels were increased in the myocardial tissues of ISO group rats, and after HDD adminis- tration, the above expression levels were decreased in group ISO, I-IDD for myocardial tissue after administration of STIM1, TRPC1, p- CaN, p-NFATc3 and NFATc3 expression decreased （P 〈 0. 05）. Our findings indicated that HDD can attenuate the myocardial remod- eling induced by ISO, and its mechanism may be related to down-regulating the expression levels of STIM1, TRPC1, CaM kinases II, p-CaN/CaN and p-NFATc3/NFATc3.

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 

分 类 号：R285.5[医药卫生—中药学]