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盐酸戊乙奎醚预处理通过线粒体动力学机制为心肌缺血/再灌注损伤大鼠模型提供心脏保护。

Penehyclidine hydrochloride preconditioning provides cardiac protection in a rat model of myocardial ischemia/reperfusion injury via the mechanism of mitochondrial dynamics mechanism.

机构信息

Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.

Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.

出版信息

Eur J Pharmacol. 2017 Oct 15;813:130-139. doi: 10.1016/j.ejphar.2017.07.031. Epub 2017 Jul 26.

DOI:10.1016/j.ejphar.2017.07.031
PMID:28755984
Abstract

To investigate that penehyclidine hydrochloride (PHC) plays a cardiac protection role in myocardial ischemia/reperfusion injury (IRI) through mitochondrial dynamics mechanism. Rat model of myocardial I/R injury was established by the ligation of left anterior descending coronary artery for 30min followed by 3h perfusion. Before I/R, the rats were pretreated with or without PHC. Cardiac function was measured by echocardiography. The activities/levels of myocardial enzymes, oxidants and antioxidant enzymes were detected. Evans blue/TTC double staining was performed to assess infarct size. Cell apoptosis was evaluated by TUNEL assay. Western blot and real time fluorescent quantitative PCR was performed to analyze the expression of Drp, Mfn, Mfn. Meanwhile, the rats were given a single injection of PHC before I/R. The effects of PHC on myocardial infarct and cardiac function were investigated after 7 days post-reperfusion. Our results showed that PHC pretreatment improved imbalance of mitochondrial dynamics induced by oxidative stressor in IRI. PHC preconditioning alleviated apoptotic rate of cell by improving the imbalance of mitochondrial dynamics in IRI. Meanwhile, we showed that PHC remarkably improved cardiac function, myocardial injury by decreasing infarct size and attenuated levels of myocardial enzyme. Additionally, PHC also exerted long-term cardiac protection in a rat model of I/R injury by decreasing infarct size and improving cardiac function. These results suggested that PHC could efficiently protect the rats against I/R-induced myocardial injury via the mechanism of mitochondrial dynamics.

摘要

目的

通过线粒体动力学机制,探讨盐酸戊乙奎醚(PHC)在心肌缺血/再灌注损伤(IRI)中发挥心脏保护作用。

方法

结扎左前降支冠状动脉 30min 后再灌注 3h,建立大鼠心肌 I/R 损伤模型。在 I/R 前,用或不用 PHC 预处理大鼠。采用超声心动图测量心功能。检测心肌酶、氧化剂和抗氧化酶的活性/水平。伊文思蓝/TTC 双重染色评估梗死面积。TUNEL 检测评估细胞凋亡。Western blot 和实时荧光定量 PCR 分析 Drp、Mfn、Mfn 的表达。同时,在 I/R 前给予大鼠单次注射 PHC,观察 PHC 对再灌注后 7 天心肌梗死和心功能的影响。

结果

PHC 预处理可改善 IRI 中氧化应激诱导的线粒体动力学失衡。PHC 预处理通过改善 IRI 中线粒体动力学失衡,减轻细胞凋亡率。此外,我们还发现,PHC 可通过减少梗死面积和减轻心肌酶水平,显著改善 I/R 损伤大鼠的心功能和心肌损伤。此外,PHC 还通过线粒体动力学机制,在 I/R 损伤大鼠模型中发挥长期的心脏保护作用,减少梗死面积,改善心功能。

结论

PHC 可有效保护大鼠免受 I/R 诱导的心肌损伤,其机制与线粒体动力学有关。

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