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多肽药物汇利心康对小鼠心肌肥大与肌球蛋白重链表达的影响
引用本文:王妍,卢小岚,杨华,李晓辉,张海港.多肽药物汇利心康对小鼠心肌肥大与肌球蛋白重链表达的影响[J].中国药学杂志,2011,46(20):1566-1569.
作者姓名:王妍  卢小岚  杨华  李晓辉  张海港
作者单位:第三军医大学药学院药剂学教研室暨新药研究中心;
基金项目:国家“重大新药创制”科技重大专项资助(2009ZX09103-052); 国家自然科学基金资助(30973524); 重庆市科技攻关项目资助(CSTC2009AB5034)
摘    要: 目的 探讨Gq蛋白羧基端模拟肽盐酸GCIP-27(汇利心康,HLXK)对去甲肾上腺素诱导的小鼠心肌肥大和肌球蛋白重链表达的影响。方法 60只小鼠,随机分为对照组、模型组、氯沙坦组、HLXK(10、30、90 μg·kg-1)组,分别给予生理盐水、去甲肾上腺素1.5 mg·kg-1(ip,bid)、氯沙坦钾9 mg·kg-1(ig,qd)、HLXK(10、30、90 μg·kg-1;ip,bid)。连续给药20 d后,称量小鼠体重、心脏质量、左心室质量,计算心脏质量指数和左心室质量指数。采用免疫组化法测定肌球蛋白重链(myosin heavy chain,MHC)α、β在心肌组织中的表达情况。结果 去甲肾上腺素可明显诱导小鼠心肌重构。氯沙坦、HLXK(30、90 μg·kg-1;bid)能明显降低小鼠心脏质量指数和左心室质量指数,增加心肌组织中α-MHC的表达,降低β-MHC的表达。结论 汇利心康能够有效防止小鼠发生心肌肥大,纠正心肌肥大过程中的肌球蛋白重链表达失衡。

关 键 词:肽类药物  GTP结合蛋白  心肌肥大  肌球蛋白重链
收稿时间:2011-11-11;

Effects of Polypeptide Drug Huilixinkang on Cardiac Hypertrophy and Expressions of Myosin Heavy Chain in Mice
WANG Yan,LU Xiao-lan,YANG Hua,LI Xiao-hui,ZHANG Hai-gang.Effects of Polypeptide Drug Huilixinkang on Cardiac Hypertrophy and Expressions of Myosin Heavy Chain in Mice[J].Chinese Pharmaceutical Journal,2011,46(20):1566-1569.
Authors:WANG Yan  LU Xiao-lan  YANG Hua  LI Xiao-hui  ZHANG Hai-gang
Institution:WANG Yan,LU Xiao-lan,YANG Hua,LI Xiao-hui,ZHANG Hai-gang*(Institute of Materia Medica and Department of Pharmaceutics,College of Pharmacy,Third Military Medical University,Chongqing 40038,China)
Abstract:OBJECTIVE To explore the effects of Huilixinkang (HLXK), a mimetic polypeptide of Gq protein carboxyl terminus, on myocardial hypertrophy and expressions of myosin heavy chain (MHC) in mice. METHODS Sixty mice were randomly divided into 6 groups, ie control, model, losartan and HLXK (10, 30, 90 μg·kg-1) groups; and administrated with normal saline, noradrenaline 1.5 mg·kg-1 (ip, bid), losartan 9 mg·kg-1 and HLXK 10, 30, 90 μg·kg-1 (ip, bid), respectively. After 20 days′ treatment, all the mice were killed, and the cardiac hypertrophy indexes including heart weight index and left ventricular mass index were measured. The expressions of α-MHC and β-MHC in myocardium were determined using immunohistochemistry technique. RESULTS Noradrenaline could induce cardiac hypertrophy in mice significantly. Losartan 9 mg·kg-1, HLXK (30, 90 μg·kg-1) markedly decreased heart weight index and left ventricular mass index, elevated the expression of α-MHC and decreased the expression of β-MHC in myocardium. CONCLUSION HLXK can effectively prevent cardiac hypertrophy in mice, and balance the expression of myosin heavy chain in the process of myocardial hypertrophy.
Keywords:polypeptide drug  GTP-binding proteins  cardiac hypertrophy  myosin heavy chain  
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