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

Effects of Polypeptide Drug Huilixinkang on Cardiac Hypertrophy and Expressions of Myosin Heavy Chain in Mice

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、90μg.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、90μg.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 heavychain,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、90μg.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。

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.