二甲双胍可减轻高同型半胱氨酸血症诱导的心肌肥厚中的心肌纤维化和细胞凋亡。
Metformin decreased myocardial fibrosis and apoptosis in hyperhomocysteinemia -induced cardiac hypertrophy.
作者信息
Zhao Qinshuo, Song Wei, Huang Jingqiu, Wang Dong, Xu Changwu
机构信息
Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
Department of Pharmacy, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
出版信息
Curr Res Transl Med. 2021 Jan;69(1):103270. doi: 10.1016/j.retram.2020.103270. Epub 2020 Oct 23.
BACKGROUND
Hyperhomocysteinemia (HHcy) is one of the major risk factors of cardiovascular diseases. Metformin acts as a cardioprotective role in several cardiovascular diseases, including ischemia/reperfusion, atherosclerosis, and myocardial infarction. However, whether metformin protects against HHcy-induced cardiac hypertrophy is unclear.
METHODS AND RESULTS
HHcy model was established in C57BL/6 mice with high L-methionine (L-MET) diet for 12 weeks. AC16 cells were exposed to homocysteine (Hcy) and then intervened with different concentrations of metformin in in vitro studies. The results showed that HHcy was able to induce cardiac hypertrophy, and metformin could abrogate this effect. HHcy increased the fibrosis area and induced apoptosis in the myocardium, whereas metformin could reverse the detrimental effects above. TUNEL assay showed that metformin was able to decrease Hcy-induced apoptosis in AC16 cells. Moreover, western blotting assay revealed that metformin could decrease Hcy-induced expression of Bax and cleaved caspase3, and increase the expression of Bcl-2.
CONCLUSIONS
This study demonstrates that metformin is able to attenuate HHcy-induced cardiac hypertrophy by decreasing myocardial fibrosis and apoptosis.
背景
高同型半胱氨酸血症（HHcy）是心血管疾病的主要危险因素之一。二甲双胍在包括缺血/再灌注、动脉粥样硬化和心肌梗死在内的多种心血管疾病中发挥心脏保护作用。然而，二甲双胍是否能预防HHcy诱导的心脏肥大尚不清楚。
方法与结果
通过给C57BL/6小鼠喂食高L-蛋氨酸（L-MET）饮食12周建立HHcy模型。在体外研究中，将AC16细胞暴露于同型半胱氨酸（Hcy），然后用不同浓度的二甲双胍进行干预。结果表明，HHcy能够诱导心脏肥大，而二甲双胍可以消除这种作用。HHcy增加了心肌纤维化面积并诱导心肌细胞凋亡，而二甲双胍可以逆转上述有害作用。TUNEL检测表明，二甲双胍能够减少Hcy诱导的AC16细胞凋亡。此外，蛋白质印迹分析显示，二甲双胍可以降低Hcy诱导的Bax和裂解的caspase3的表达，并增加Bcl-2的表达。
结论
本研究表明，二甲双胍能够通过减少心肌纤维化和细胞凋亡来减轻HHcy诱导的心脏肥大。
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