基础医学与临床 ›› 2021, Vol. 41 ›› Issue (7): 935-940.

• 研究论文 •    下一篇

Ghrelin改善ApoE-/-小鼠心肌梗死后内皮功能和斑块稳定性

王丽1,庞俊1,陈庆伟2,李桂琼3,柯大智4,李兴升1   

  1. 1. 重庆医科大学第二临床学院
    2. 重庆医科大学附属第二医院
    3. 重庆医科大学附属第二医院老年病科
    4. 重庆医科大学第二附属医院
  • 收稿日期:2019-11-15 修回日期:2020-11-10 出版日期:2021-07-05 发布日期:2021-06-17
  • 通讯作者: 陈庆伟 E-mail:chenqwcq@126.com
  • 基金资助:
    Ghrelin对动脉粥样硬化易损斑块内血管新生和斑块稳定性的影响及机制研究;Ghrelin对动脉粥样硬化易损斑块内皮细胞/周细胞稳定性的影响及机制研究

Ghrelin improves endothelial function and plaque stability after myocardial infarction in ApoE-/- mice

  • Received:2019-11-15 Revised:2020-11-10 Online:2021-07-05 Published:2021-06-17

摘要: 目的 探讨ghrelin对ApoE-/-小鼠心梗后内皮功能和斑块稳定性的影响及机制研究。方法 将ApoE-/-小鼠分为对照组、双模型组和ghrelin干预组。所有ApoE-/-小鼠均高脂饮食喂养12周诱导动脉粥样硬化易损斑块,构建的动脉粥样硬化易损斑块模型即为对照组。在第8周时,双模型组和ghrelin干预组结扎冠状动脉左前降支构建急性心梗模型。在急性心梗造模后,ghrelin干预组腹腔注射ghrelin(100μg/kg,一天两次),直至第12周实验结束。检测体质量、血脂,超声心动图检测左心室射血分数(LVEF)和左心室短轴缩短率(LVFS),Griess法检测一氧化氮(NO)水平,HE染色观察主动脉斑块面积占管腔面积的百分比,行油红0和苦味酸天狼猩红染色观察斑块内脂质和胶原的分布,应用RAM-11及a-actin免疫组化染色分别测定斑块内巨噬细胞、平滑肌细胞的分布,计算易损指数。Masson染色检测心肌梗死面积,实时荧光定量PCR和Westernblot分别检测血管内皮细胞生长因子(vascular endothelial growth factor, VEGF)mRNA和蛋白表达。结果 与对照组相比,双模型组LVEF和LVFS、血清NO2` / NO3` 水平降低(P<0.05),VEGF的表达增加(P<0.05)。Ghrelin干预后可显著降低双模型组血浆TG水平和心肌梗死面积(P<0.05),升高EF、FS、血浆NO2` / NO3` 水平及VEGF的表达(P<0.05),增加斑块内胶原纤维和平滑肌细胞的分布(P<0.05),降低主动脉窦粥样斑块面积的百分比、及斑块内脂质和巨噬细胞的分布(P<0.05),减低易损指数(P<0.05)。结论 1)ghrelin可改善ApoE-/-小鼠心肌梗死后血管内皮功能、提高心功能;2)ghrelin可促进易损斑块的稳定性,减少再梗死发生。

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

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