关键词: ghrelin, 易损斑块, 心肌梗死, 内皮功能, ApoE-/-小鼠

Abstract: Objective To investigate the effects and mechanisms of ghrelin on plaque stability and endothelial funtion in ApoE-/- mice after myocardial infarction. Methods The ApoE-/- mice were divided into control group, double model group and ghrelin-treated group. All ApoE-/- mice were fed a high-fat diet for 12 weeks to induce atherosclerotic vulnerable plaques. The atherosclerotic vulnerable plaque model was the control group.At the 8th week of this study, the double model group and the ghrelin group were subjected to acute myocardial infarction model(AMI). After modeling of AMI, the ghrelin group were administered ghrelin (100μg/kg，bid) until the end of the 12th week. Body weight and blood lipids were detected. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were detected by echocardiography, NO level was measured by Griess method, and the percentage of aortic sinus plaque area was evaluated by HE staining. The plaque content of lipid and collagen was observed by oil red 0 and Sirius red staining. The distribution of macrophages and smooth muscle cells in plaques were determined by RAM-11 and a-actin immunohistochemical staining. And then we calculate the vulnerability index. Myocardial infarct size was detected by Masson staining. The vascular endothelial growth factor (VEGF) was detected by quantitative real-time PCR and Western-blot. Results Compared with the control group, the levels LVEF and LVFS, and NO2` / NO3` concentration in the double model group were decreased, and the expression of VEGF was increased, significantly. However, the ghrelin group had significantly reduced plasma TG levels and myocardial infarct size, and improved the LVEF and LVFS, the NO2` / NO3` level, the expression of VEGF， the plaque content of collagen and smooth muscle cells, and reduced the percentage of aortic sinus plaque area, the distribution of lipid and macrophages, and the vulnerability index compared with the double model group. Conclusions 1) Ghrelin is able to improve the endothelial function and increase heart function in ApoE-/- mice after myocardial infarction. 2) Ghrelin can stabilize vulnerable plaque and reduce the occurrence of reinfarction.

Key words: ghrelin, vulnerable plaque, myocardial infarction, endothelial function, ApoE-/- mice