PINK1/Parkin信号通路介导的线粒体自噬在重症肺炎中的作用研究

Role of mitochondrial autophagy mediated by PINK1/Parkin signaling pathway in severe pneumonia

目的探究PINK1(同源性磷酸酶张力蛋白诱导激酶1)/Parkin(帕金森蛋白)信号通路介导的线粒体自噬在大鼠重症肺炎中的作用。方法将20只大鼠随机分为对照组及模型组(重症肺炎模型),每组10只,以探讨重症肺炎对大鼠肺功能、病理的影响。之后再将30只大鼠随机分为对照组、模型组及mdivi-1(线粒体自噬抑制剂)组,每组10只,进一步探讨重症肺炎对大鼠线粒体自噬指标的影响。结果与对照组相比,模型组大鼠静息通气量[(3.44±0.22)vs.(1.58±0.18)mL/min]及气道阻力比值(77.48±3.84 vs.47.76±5.54)降低(P<0.05);模型组大鼠肺组织损伤,可见大量炎性细胞浸润;模型组大鼠肺组织中Parkin、PINK1及微管相关蛋白1轻链3Ⅱ的蛋白和mRNA表达水平增加(P<0.05)。与模型组相比,mdivi-1组大鼠静息通气量及气道阻力比值增加(P<0.05);mdivi-1组大鼠肺组织损伤及炎性浸润改善;mdivi-1组大鼠肺组织中Parkin、PINK1及微管相关蛋白1轻链3Ⅱ的蛋白和mRNA表达水平减少(P<0.05)。结论mdivi-1可改善重症肺炎大鼠肺功能结构的异常,其机制可能与PINK1/Parkin信号通路介导的线粒体自噬相关。

Objective To investigate the role of mitochondrial autophagy mediated by PINK1(homologous phosphatase tensin induced kinase 1)/Parkin(Parkinson’s protein)signaling pathway in severe pneumonia of rats.Methods Twenty rats were randomly divided into control group and model group(severe pneumonia model),with 10 rats in each group,to explore the effects of severe pneumonia on lung function and pathology in rats.Then,30 rats were randomly divided into control group,model group and mdivi-1(mitochondrial autophagy inhibitor)group,with 10 rats in each group,to further explore the effects of severe pneumonia on mitochondrial autophagy indicators of rats.Results Compared with the control group,the resting ventilation volume[(3.44±0.22)vs.(1.58±0.18)mL/min]and airway resistance ratio(77.48±3.84 vs.47.76±5.54)in the model group were decreased(P<0.05).In the model group,the lung tissue was injured and a large number of inflammatory cells were infiltrated.The protein and mRNA expression levels of Parkin,PINK1 and microtubule-associated protein1 light chain 3 in lung tissues of model group were increased(P<0.05).Compared with model group,the ratio of resting ventilator-to-airway resistance in mdivi-1 group increased(P<0.05).The injury and inflammatory infiltration of lung tissue were improved in mdivi-1 group.The expression levels of Parkin,PINK1 and microtubule-associated protein1 light chain 3 protein and mRNA in lung tissues of mdivi-1 group were decreased(P<0.05).Conclusion Mdivi-1 can improve the abnormal lung function structure in rats with severe pneumonia,and the mechanism may be related to mitochondrial autophagy mediated by PINK1/Parkin signaling pathway.