张军 王巧玲 郭菲菲 孙向荣 韩晓华 公衍玲 刘虹 杨南 徐珞.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[J].,2014,14(32):6237-6241 |
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 andCardiac Function after Infarction |
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DOI: |
中文关键词: Ghrelin 心肌梗死 白介素-1beta 肿瘤坏死因子-alpha 基质金属蛋白酶-2 基质金属蛋白酶-9 |
英文关键词: Ghrelin Myocardial infarction IL-1beta TNF-alpha MMP-2 MMP-9 |
基金项目: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) |
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中文摘要: |
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 (100 ug/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)-1beta、肿瘤坏死因子-alpha(TNF-alpha)、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)-1beta、肿瘤坏死因子-alpha(TNF-alpja)、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。 |
英文摘要: |
Objective:To study the effects of ghrelin on the heart function 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 MI. In MI-ghrelin group, ghrelin (100ug/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)-1b, tumor necrosis factor-a (TNF-alpha), 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)-1band tumor necrosis factor-alpha(TNF-alpha). Subsequently, the expression of matrix metalloproteinase (MMP)-2 and MMP-9
were also inhibited by ghrelin injection.Conclusion:Ghrelin alleviated LV dysfunction and ventricular remodeling of post-MI rats, which
might be contributed by the inflamination-inhibiting effect of ghrelin. |
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