通心络胶囊对热射病大鼠心肌细胞线粒体自噬及PINK1/Parkin通路的影响  

Effects of Tongxinluo capsule on mitochondrial autophagy and PINK1/Parkin pathway in myocardial cells of heat stroke rats

作　　者：哈斯叶提·吐尔逊 艾尔西丁·吾斯曼[1] 吴长东[1] Hasyeti Turson;Elsitin Usman;Wu Changdong(Emergency Center,Xinjiang Uygur Autonomous Region People's Hospital,Urumqi 830001,China)

机构地区：[1]新疆维吾尔自治区人民医院急救中心,乌鲁木齐830001

出　　处：《广西医科大学学报》2021年第8期1511-1516,共6页Journal of Guangxi Medical University

基　　金：新疆维吾尔自治区自然科学基金项目(No.2020D01C106,2016D01C113)。

摘　　要：目的:探讨通心络胶囊对热射病大鼠心肌细胞线粒体自噬及PTEN诱导假定激酶1(PINK1)/Parkin通路的影响。方法:制备经典型热射病大鼠模型,随机分为模型组、通心络低剂量组(0.1 g/kg)、通心络中剂量组(0.3 g/kg)、通心络高剂量组(0.9 g/kg),另取正常大鼠作为对照,记为正常组。采用酶联免疫吸附试验(ELISA)法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6水平;苏木精—伊红(HE)染色观察心肌组织病理改变;透射电子显微镜观察心肌细胞线粒体自噬;TUNEL法检测心肌细胞凋亡;Western blotting法检测心肌组织PINK1/Parkin通路蛋白以及微管相关蛋白轻链3(LC3)、p62、Beclin1自噬相关蛋白水平。结果:正常组心肌组织结构、线粒体结构均正常,自噬极少;模型组心肌细胞排列紊乱,形态不规则,线粒体肿胀,结构紊乱,出现自噬;通心络各剂量组心肌细胞排列较为整齐,线粒体形态结构相对完好,自噬现象明显。与正常组比较,模型组心肌细胞凋亡率,血清TNF-α、IL-1β、IL-6水平,LC3-Ⅱ/LC3-Ⅰ比值及p62、PINK1、Parkin蛋白表达量均显著升高(P<0.05);与模型组比较,通心络各剂量组心肌细胞凋亡率和TNF-α、IL-1β、IL-6水平以及p62蛋白表达均显著降低,LC3-Ⅱ/LC3-Ⅰ、Beclin1、PINK1、Parkin蛋白表达均显著升高(P<0.05)。结论:通心络胶囊可能通过进一步激活PINK1/Parkin通路,加强热射病大鼠心肌细胞线粒体自噬水平,抑制心肌组织炎症反应,对心肌细胞起到保护作用。Objective:To investigate the effects of Tongxinluo capsule on mitochondrial autophagy and PTEN induced putative kinase 1(PINK1)/Parkin pathway in myocardial cells of heat stroke rats.Methods:The classical heat stroke rat models were established and randomly divided into model group,low-dose Tongxinluo group(0.1 g/kg/d),medium-dose Tongxinluo group(0.3 g/kg/d)and high-dose Tongxinluo group(0.9 g/kg/d).Healthy rats were defined as normal group.The levels of serum tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 were detected by enzyme-linked immunosorbent assay(ELISA);the pathological changes of myocardium were observed by hematoxylin eosin(HE)staining;mitochondrial autophagy was observed by transmission electron microscope;cardiomyocyte apoptosis was detected by TUNEL;the levels of PINK1/Parkin pathway protein,microtubule associated protein light chain 3(LC3),p62 and Beclin1 were detected by Western blotting.Results:In the normal group,the structure of myocardial tissue and mitochondria were normal,and autophagy was rare;in the model group,the arrangement of myocardial cells was disordered,the shape was irregular,the mitochondria swelled,the structure was disordered,and autophagy appeared;in Tongxinluo groups,the arrangement of cardiomyocytes was more orderly,the morphology and structure of mitochondria were relatively intact,and autophagy was obvious.Compared with the normal group,the apoptosis rate of cardiomyocytes,the levels of TNF-α,IL-1β,IL-6,LC3-Ⅱ/LC3-Ⅰratio,and the protein expression of p62,PINK1 and Parkin in the model group were significantly increased(P<0.05);compared with the model group,the apoptosis rate of cardiomyocytes,the levels of TNF-α,IL-1βand IL-6 and the protein expression of p62 in Tongxinluo groups were significantly decreased,whereas the LC3-Ⅱ/LC3-Ⅰratio and the protein expression of Beclin1,PINK1 and Parkin was significantly increased(P<0.05).Conclusion:Tongxinluo capsule has a protective effect on cardiomyocytes,and it can promote mitochondrial autophagy and inh

关 键 词：通心络 热射病 心肌细胞 线粒体自噬 PINK1/Parkin通路 

分 类 号：R259[医药卫生—中西医结合]