外源性生长激素释放肽通过调节腺苷酸活化蛋白
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高等学校博士学科点专项科研基金(20112104120002)


Effects of Exogenous Ghrelin Through Regulation of AMP-Activated Protein Kinase Pathway Improves Cardiac Function in Rats
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    摘要:

    目的 探索生长激素释放肽(Ghrelin)的心脏保护效应机制,明确外源性Ghrelin是否通过调节腺苷酸活化蛋白激酶(AMPKα2)及葡萄糖转运蛋白4(Glut4)表达而改善自发性糖尿病大鼠(GK)心脏功能。方法 GK大鼠编号随机分为3组:GK组、二甲双胍组(二甲双胍灌胃4周)和Ghrelin组(外源性 Ghrelin 腹腔注射4周),另选Wistar大鼠为对照。通过透射电镜观察大鼠心肌超微结构;应用多道生理记录仪观察大鼠心脏功能;留取大鼠动脉血液计算胰岛素抵抗指数(HOMA-IR);采用RT-PCR 法测量AMPKα2 及Glut4基因表达。结果 实验4周后,与Wistar组及GK组比较,Ghrelin组心率降低,舒张、收缩功能改善(P<0.05);Ghrelin组大鼠的HOMA-IR指数低于GK组(P<0.05);Ghrelin组大鼠心肌内线粒体及心肌间微血管接近Wistar组;Ghrelin及二甲双胍干预后大鼠心肌AMPKα2和Glut4 mRNA表达量有明显增加(P<0.05)。结论 Ghrelin腹腔注射可减轻自发性糖尿病大鼠胰岛素抵抗,提高自发性糖尿病大鼠心脏左心室舒张和收缩功能,其机制可能与较长期在体上调心肌细胞AMPK表达而促进葡萄糖转运有关。

    Abstract:

    Aim To observe the role of Ghrelin on myocardial metabolism key enzyme AMP-activated protein kinase (AMPK) signaling pathway. Methods Goto-Kakizaki (GK) rats (8-week-old males) were randomly divided into three groups with 8 rats in each group: GK group,metformin group(received metformin 350 mg/kg),and Ghrelin group (received Ghrelin 200 μg/kg in twice daily). Normal male Wistar kyoto rats (n8) served as normal controls. Four weeks later,the effects of Ghrelin on cardiac remodeling were evaluated by echocardiographic,hemody- namicand gene expression analysis (AMPK,Glut4 mRNA expression). Results After 4 weeks,compared with Wistar rats and GK group,heart rate reduced,diastolic,systolic function improved in Ghrelin group (P<0.05) HOMA-IR index was lower than the GK rats in Ghrelin group (P<0.05) Myocardial mitochondria and myocardial microvascular of Ghrelin group rats were close to Wistar group. Myocardial AMPKα2,Glut4 mRNA expression levels were significantly increased in Ghrelin group compared with GK group (P<0.05). Conclusions Intraperitoneal injection of Ghrelin can reduce the spontaneous GK rats insulin resistance,and improve left ventricular diastolic and systolic function. Its mechanism may be associated with longer-term increase of AMPK expression of myocardial cell and the promotion of the glucose transporter.

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李 昭,白英龙,胡文宇,孙英贤, 胡健.外源性生长激素释放肽通过调节腺苷酸活化蛋白[J].中国动脉硬化杂志,2013,21(02):139~143.

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  • 收稿日期:2012-08-02
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