参附益心颗粒对急性心肌梗死后心力衰竭大鼠心肌细胞线粒体自噬的影响
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篇名: 参附益心颗粒对急性心肌梗死后心力衰竭大鼠心肌细胞线粒体自噬的影响
TITLE: Effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute yocardial infarction
摘要: 目的 研究参附益心颗粒对急性心肌梗死后心力衰竭大鼠心肌细胞线粒体自噬的影响。方法采用结扎左冠状动脉前降支的方法建立急性心肌梗死后心力衰竭大鼠模型,将造模成功的大鼠分为模型组,参附益心颗粒低、高剂量组(1.76、8.8g/kg),福辛普利钠片组(阳性对照,4mg/kg),另设假手术组(相同位置只穿线不结扎),每组8只。干预4周后,使用生理记录仪检测各组大鼠的血流动力学指标,观察各组大鼠心肌组织的病理学变化,检测各组大鼠心肌细胞氧化应激水平和线粒体膜电位以及心肌组织中PTEN诱导激酶1(PINK1)、E3泛素连接酶Parkin、泛素结合蛋白P62的表达水平。结果与假手术组比较,模型组大鼠心肌纤维形态紊乱,炎症细胞浸润等病理损伤严重,其左心室收缩末期压力(LVESP)、左心室内压最大上升速率(+dp/dtmax)、左心室内压最大下降速率(-dp/dtmax)、左心室缺血心肌细胞总抗氧化能力、线粒体膜电位以及心肌组织中PINK1、Parkin、P62蛋白的表达水平均显著降低(P<0.01),左心室舒张末期压力(LVEDP)、左心室缺血心肌细胞活性氧水平和还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性均显著升高(P<0.01)。与模型组比较,各药物干预组大鼠心肌组织病理损伤有所减轻,上述指标均有不同程度改善(P<0.01或P<0.05)。结论参附益心颗粒具有降低氧化应激水平、缓解急性心肌梗死后心力衰竭的作用,可能与其激活Parkin依赖性通路而增强线粒体自噬、减少线粒体功能障碍有关。
ABSTRACT: OBJECTIVE To study the effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute myocardial infarction. METHODS The model of heart failure after acute myocardial infarction was established by ligaturing the anterior descending branch of the left coronary artery in rats. The model rats were divided into model group,Shenfu yixin granule low-dose and high-dose groups (1.76,8.8 g/kg),Fosinopril sodium tablets group (positive control ,4 mg/kg),sham operation group was set up (only threading without ligation at the same position ),with 8 rats in each group. After 4 weeks of drug intervention ,the hemodynamic indexes of rats in each group were measured by physiological recorder. The pathological changes of myocardial tissue were observed in each group. The level of oxidative stress in cardiomyocytes , mitochondrial membrane potential ,protein expression of PTEN-induced putative kinase 1(PINK1),E3 ubiquitin ligase Parkin and ubiquitin binding protein P 62 in myocardial tissue of rats in each group were detected. RESULTS Compared with sham operation group ,the pathological injuries such as myocardial fiber morphology disorder and inflammatory cell infiltration were serious. The left ventricular end systolic pressure (LVESP),maximum rate of rise of left ventricular internal pressure (+dp/dtmax), maximun rate of decrease of left ventricular internal pressure (-dp/dtmax),total antioxidant capacity ,mitochondrial membrane potential,PINK1,Parkin and P 62 protein expression were significantly decreased in model group (P<0.01). The left ventricular end diastolic pressure (LVEDP),the level of reactive oxygen species and the activity of reduced nicotinamide adenine dinucleotide phosphate in left ventricular ischemic cardiomyocytes were significantly increased (P<0.01). Compared with model group ,the pathological injuries of myocardial tissue in intervention groups were alleviated ,and above indexes were improved in varying degrees(P<0.01 or P<0.05). CONCLUSIONS Shenfu y ixin granule can reduce the level of oxidative stress and alleviate heart failure after acute myocardial infarction ,which may be related to the activation of Parkin-dependent pathway to strengthen mitochondrial autophagy and reduce mitochondrial dysfunction.
期刊: 2022年第33卷第10期
作者: 曹亚选,郑荣菲,王贺,曹英杰,董文杰,崔琳,李彬,陈玉善,朱明军
AUTHORS: CAO Yaxuan, ZHENG Rongfei,WANG He,CAO Yingjie,DONG Wenjie,CUI Lin,LI Bin,CHEN Yushan,ZHU Mingjun
关键字: 参附益心颗粒;急性心肌梗死;心力衰竭;线粒体自噬;大鼠
KEYWORDS: Shenfu yixin granule ; acute myocardial
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