异氟醚经Pink1/Parkin信号通路激活线粒体自噬对小鼠心肌缺血再灌注的保护作用  

Protective effect of isoflurane on myocardial ischemia-reperfusion injury in mice through activation of mitochondrial autophagy via the Pink1/Parkin signaling pathway

作　　者：梁进伟[1] 刘楚云 吴珊瑚[1] 孙亚锋[2] Liang Jinwei;Liu Chuyun;Wu Shanhu;Sun Yafeng(Anesthesiology Department of the Second Affiliated Hospital of Fujian Medical University,Quan Zhou 362000,China;Department of Gastroenterology,The Second Affiliated Hospital of Fujian Medical University,Quan Zhou 362000,China)

机构地区：[1]福建医科大学附属第二医院麻醉科,泉州362000 [2]福建医科大学附属第二医院胃肠外科,泉州362000

出　　处：《中国组织化学与细胞化学杂志》2023年第6期554-561,共8页Chinese Journal of Histochemistry and Cytochemistry

基　　金：泉州市科技计划项目(2018Z128)。

摘　　要：目的 探究异氟醚(isoflurane, ISO)通过Pink1/Parkin信号通路对小鼠心肌缺血再灌注(ischemia-reperfusion,IR)损伤中线粒体自噬的影响。方法 本研究建立小鼠心肌IR模型,并将24只小鼠分为4组:假手术(Sham)组、假手术+异氟醚(Sham+ISO)组、缺血再灌注(IR)组、缺血再灌注+异氟醚(IR+ISO)组。通过HE染色评估心肌组织损伤,利用TUNEL染色观察心肌细胞凋亡,通过Western blot检测心肌细胞线粒体自噬相关蛋白(包括Pink1、parkin、Beclin、P62和LC3)的表达,并使用相关试剂盒测定心肌细胞线粒体内膜电位及ATP含量。结果 与Sham组相比,IR组的心肌细胞损伤更为严重,心肌组织损伤评分增加,细胞凋亡率升高。线粒体自噬相关蛋白表达紊乱,线粒体内膜电位和ATP含量显著下降。值得注意的是,在ISO处理的IR小鼠中,IR损伤导致的心肌组织损伤评分和心肌细胞凋亡率明显减轻;线粒体自噬相关蛋白的表达部分恢复,线粒体内膜电位和ATP含量的降低也得到了显著改善。结论 ISO可以通过Pink1/Parkin信号通路抑制小鼠心肌组织中的线粒体自噬,而在心肌IR模型中,ISO能部分激活线粒体自噬,从而对IR引起的心肌组织损伤起到保护作用。Objective To explore the effect of isoflurane(ISO)on mitochondrial autophagy in myocardial ischemia-reperfusion(IR)injury in mice through the Pink1/Parkin signaling pathway.Methods This study established a mouse model of myocardial IR and divided 24 mice into four groups:sham operation(Sham)group,sham operation plus isoflurane(Sham+ISO)group,ischemia-reperfusion(IR)group,and ischemia-reperfusion plus isoflurane(IR+ISO)group.Myocardial tissue damage was evaluated by HE staining,myocardial cell apoptosis was observed by TUNEL staining,and the expression of mitochondrial autophagy-related proteins(including Pink1,parkin,Beclin,P62,and LC3)was detected by Western blot.Mitochondrial inner membrane potential and ATP content in myocardial cells were also measured using relevant kits.Results Compared with the Sham group,the IR group showed more severe myocardial cell damage,increased myocardial tissue damage scores,and higher cell apoptosis rates.There was disordered expression of mitochondrial autophagy-related proteins,and significant reductions in mitochondrial inner membrane potential and ATP content.Notably,in the IR mice treated with ISO,the IR injury-induced increases in myocardial tissue damage scores and myocardial cell apoptosis rates were significantly mitigated.Furthermore,there was partial restoration in the expression of mitochondrial autophagy-related proteins,and the reductions in mitochondrial inner membrane potential and ATP content were significantly improved.Conclusion ISO can inhibit mitochondrial autophagy in myocardial tissues of mice through the Pink1/parkin signaling pathway.However,in the myocardial IR model,ISO can partially activate mitochondrial autophagy,thereby protecting the myocardial tissue from IR-induced damage.

关 键 词：异氟醚 Pink1/Parkin 缺血再灌注 线粒体自噬 

分 类 号：R365[医药卫生—病理学]