重组人胰岛素样生长因子-Ι对心肌梗死大鼠心肌基质金属蛋白酶表达及心肌间质降解的影响

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (8): 866-871.

重组人胰岛素样生长因子-Ι对心肌梗死大鼠心肌基质金属蛋白酶表达及心肌间质降解的影响

蔚有权, 曹蘅

皖南医学院弋矶山医院心血管内科,芜湖 241001,安徽

收稿日期:2014-05-08 修回日期:2014-07-21 出版日期:2014-08-26 发布日期:2014-08-26
通讯作者: 曹蘅,女,教授,硕士生导师,研究方向:心血管疾病诊治及心血管药物治疗学。 Tel: 0553-5739552 E-mail: yjscaoheng@163.com
作者简介:蔚有权,男,硕士,主治医师,研究方向:心血管药物治疗学。 Tel: 0553-5739550 E-mail: cardio_wei@163.com

Effects of recombinant human insulin-like growth factor-Ι on the expression of matrix metalloproteinases and interstitial degradation of myocardial infarction rats

WEI You-quan, CAO Heng

Department of Cardiology, Yijishan Hospital of Wannan Medical College,Wuhu 241001, Anhui, China

Received:2014-05-08 Revised:2014-07-21 Online:2014-08-26 Published:2014-08-26

摘要/Abstract

摘要： 目的探讨重组人胰岛素样生长因子-Ι(rhIGF-Ι)对心肌梗死(MI)大鼠心肌基质金属蛋白酶(MMPs)的表达及心肌间质降解的影响。方法 48只SD大鼠腹腔注射异丙基肾上腺素建立MI模型后随机分成3组,每组16只,术后分别给予rhIGF-Ι 50 μg·kg^-1·d^-1(IGF-I组)、奥曲肽 50 μg·kg^-1·d^-1(Oct组)和生理盐水 5 mL·kg^-1·d^-1(MI组),每组按照用药时间(2、14 d)再分成2个亚组(分别是IGF-I_{2 d}、IGF-I _{14 d},Oct_{2 d}、Oct_{14 d},和MI_{2 d}、MI_{14 d} 组,n=8),另取8只正常SD大鼠作为阴性对照组。超声测定大鼠左室前壁(LVAW)、后壁(LVPW)厚度、左室收缩末期内径(LVESD)、左室舒张末内径(LVEDD)以及短轴缩短率(FS);大鼠处死后消化法测定心肌组织匀浆羟脯氨酸浓度;免疫组织化学法检测基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)及基质金属蛋白酶组织抑制因子-1(TIMP-1)在心肌中的表达。结果与MI组相比,IGF-I组大鼠梗死区心肌MMP-2、MMP-9活性降低,TIMP-1表达增加,心肌胶原降解减少, LVEDD、LVESD减小,FS增加;Oct组MMP-2 、MMP-9表达增加,胶原蛋白降解显著, LVAW降低,LVEDD、LVESD增加,FS下降。结论 rhIGF-Ι治疗使MI大鼠心肌MMPs活性减弱,TIMP-1表达上调,心肌间质胶原降解减少,心室重构减轻。

关键词: 胰岛素样生长因子-Ι, 心肌梗死, 心室重构, 基质金属蛋白酶, 基质金属蛋白酶组织抑制因子

Abstract: AIM: To examine the effect of recombinant human insulin-like growth factor-I(rhIGF-I) on the expression of matrix metalloproteinases (MMPs) and interstitial degradation of myocardium in postinfarction rats. METHODS: Seven-week old male Sprague-Dawley (SD) rats were intraperitoneally injected with isoprenaline to establish myocardial infarction (MI) model. Forty-eight rats showed clear ECG evidence of infarction and were assigned randomly to IGF-I group (rhIGF-I 50 μg·kg^-1·d^-1, i.v.), Oct group (Octreotide 50 μg·kg^-1·d^-1, i.v.) or MI group (normal sodium 5 mL·kg^-1·d^-1, i.v.). Each group was divided into two subgroups (n=8, respectively) according to the treatment days, 2 or 14 days when the rats were sacrificed. Another 8 normal SD rats were selected as the control group. Transthoracic echocardiograms were performed to examine the thickness of anterior wall (LVAW) and posterior wall (LVPW) of left ventricle, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), and fractional shortening (FS) as well. The levels of MMP-2, MMP-9, TIMP-1 in myocardium were quantified with immunohistochemistry. Tissue homogenate myocardium hydroxyproline concentration was determined by pepsis method.RESULTS: Compared with the MI group, the expressions of MMP-2 and MMP-9 in rhIGF-I group were decreased, and the expression of TIMP-1 in the infarcted areas was increased;the degradation of myocardium collagen were decreased and the LVEDD and LVESD were decreased, the FS was increased; the expressions of MMP-2 and MMP-9 in Oct group were increased, the degradation of myocardium collagen was aggravated, the LVAW was decreased, the LVEDD, LVESD were increased, the FS was decreased.CONCLUSION: rhIGF-I administered to rats after MI is associated with decreased activities of MMPs, substantial increase of expression of TIMP-1, and leads to attenuate interstitial degradation of myocardium and may improve ventricular remodeling.

Key words: insulin-like growth factor-I, myocardial infarction, ventricular remodeling, matrix metalloproteinase, tissue inhibitor of metalloproteinase-I

中图分类号:

R363
965.2

蔚有权, 曹蘅. 重组人胰岛素样生长因子-Ι对心肌梗死大鼠心肌基质金属蛋白酶表达及心肌间质降解的影响[J]. 中国临床药理学与治疗学, 2014, 19(8): 866-871.

WEI You-quan, CAO Heng. Effects of recombinant human insulin-like growth factor-Ι on the expression of matrix metalloproteinases and interstitial degradation of myocardial infarction rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(8): 866-871.

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