Ghrelin对心肌梗死后心肌重塑及心脏功能的影响及其机制研究  

Effects and Mechanisms of Ghrelin on the Myocardial Remodeling and Cardiac Function after Infarction

作　　者：张军[1,2] 王巧玲[1] 郭菲菲[1] 孙向荣[1] 韩晓华[1] 公衍玲[3] 刘虹[4] 杨南[4] 徐珞[1] 

机构地区：[1]青岛大学医学院病理生理学教研室,山东青岛266021 [2]菏泽市立医院,山东菏泽274031 [3]青岛科技大学化工学院,山东青岛266042 [4]青岛市立医院,山东青岛266011

出　　处：《现代生物医学进展》2014年第32期6237-6241,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(31071014;81100260;81270460;81300281);山东省医药卫生科技发展计划项目(2013WS0263);青岛市科技局项目(13-1-4-170-jch)

摘　　要：目的:观察ghrelin对心肌梗死(MI)大鼠心肌重塑和心脏功能的影响,并探讨其可能的机制。方法:应用冠状动脉结扎术创建大鼠MI模型,并设立假手术组作为对照;造模成功后每天2次注射ghrelin(100μg/kg),持续4周,以此作为MI-ghrelin组,并以每天注射生理盐水的MI大鼠作为MI-生理盐水组。检测和比较各组大鼠左心室重塑和血流动力学的改变情况;非梗死心肌中白介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶(MMP)-2、MMP-9 mRNA和蛋白的表达;梗死边界心肌细胞的凋亡情况。结果:Ghrelin可使心肌梗死后的MI大鼠降低的缩短分数(FS)、左室内压最大变化率均显著下降(dP/dtmax)、疤痕厚度明显升高,增加左室舒张末压(LVEDP)、左室收缩末内径(LVESD)、左室舒张末期内径(LVEDD)、梗死边界心肌细胞的凋亡指数显著降低。此外,ghrelin可抑制心肌梗死后的MI大鼠非梗死心肌中白介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、质金属蛋白酶(MMP)-2和MMP-9的mRNA和蛋白的表达。结论:Ghrelin可缓解MI后大鼠LV功能紊乱及心室重塑,这可能与其抑制炎症反应及基质金属蛋白酶的表达有关。Objective： To study the effects of ghrelin on the heart fimction and myocardial remodeling of myocardial infarction rats, and discuss the mechanisms of ghrelin on myocardial protection. Methods： Ligation of a coronary artery was used to create a rat model of M1. In MI-ghrelin group, ghrelin （100μg/kg） was injected twice a day for 4 weeks; while saline was injected in the rats of MI-saline group. The following items were examined： the remodeling of left ventricle and hemodynamics, mRNA and protein levels of interleukin （IL）-lb, tumor necrosis factor-a （TNF-α, matrix metalloproteinase （MMP）-2 and MMP-9 in non-infarcted myocardium, and the apoptosis of the cardiomyocytes in the infarcted border. Results： Compared with sham group, ghrelin administration significantly decreased the left ventricular （LV） remodeling of post-MI rats, as indicated by increased LV maximum rate of pressure, LV fractional shortening and scar thickness; and decreased LV end-diastolic pressure, LV end-systolic diameter, LV end-diastolic diameter and cardiocytocytes apoptosis. Moreover, ghrelin inhibited the inflammatory response, as shown by decreased mRNA and protein levels of interleukin （IL）-lband tumor necrosis factor-α （TNF-α）. Subsequently, the expression of matrix metalloproteinase （MMP）-2 and MMP-9 were also inhibited by ghrelin injection. Conclusion： Ghrelin alleviated LV dysfimction and ventficular remodeling ofpost-MI rats, which might be contributed by the inflamination-inhibiting effect of ghrelin.

关 键 词：GHRELIN 心肌梗死 白介素-1Β 肿瘤坏死因子-α 基质金属蛋白酶-2 基质金属蛋白酶-9 

分 类 号：Q95-3[生物学—动物学] R542.22[医药卫生—心血管疾病]