医学
缺血预处理
细胞凋亡
内科学
缺血
肝硬化
二甲双胍
心脏病学
内分泌学
结扎
药理学
生物
生物化学
胰岛素
作者
Hamid Reza Moheimani,Taghi Amiriani,Ali Mohammad Alizadeh,Yahya Jand,Delaram Shakiba,Parham Sayyah Ensan,Fatemeh Jafarzadeh,Maryam Rajaei,Ahmad Ali Enayati,Mona Pourabouk,Shahriar Aliazadeh,Amir Hoshang Pourkhani,Zohreh Mazaheri,Mohammad Ali Zeyghami,Ahmad Reza Dehpour,Vahid Khori
标识
DOI:10.1016/j.ejphar.2020.173807
摘要
Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats’ hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria.
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