大蒜素调控PINK1/Parkin介导的线粒体自噬改善大鼠尿毒症心肌损伤  

Allicin Modulates PINK1/Parkin-Mediated Mitochondrial Autophagy to Improve Uremic-Induced Myocardial Injury in Rats

作　　者：沈金峰 胡芳 王福珍 廖思霖 江辉 SHEN Jinfeng;HU Fang;WANG Fuzhen;LIAO Silin;JIANG Hui(Longyan First Hospital Affiliated to Fujian Medical University,Longyan 364000 Fujian,China;Longyan Hospital of Traditional Chinese Medicine Affiliated to Xiamen University,Longyan 364000 Fujian,China)

机构地区：[1]福建医科大学附属龙岩第一医院,福建龙岩364000 [2]厦门大学附属龙岩市中医院,福建龙岩364000

出　　处：《广州中医药大学学报》2025年第2期448-454,共7页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：福建省自然科学基金项目(编号:2023J011898);龙岩市科技计划项目(编号:FLY2022CWS010098);福建医科大学启航基金项目(编号:2022QH1340)。

摘　　要：【目的】观察大蒜素对尿毒症心肌损伤大鼠的治疗作用及机制。【方法】将24只大鼠随机分为假手术组,模型组,大蒜素低、高剂量组,每组6只。除假手术组,其他各组大鼠采用5/6肾切除法构建尿毒症心肌损伤模型。造模成功后,给予相应干预。干预结束后,观察大鼠肾功能,计算心脏质量指数,酶联免疫吸附分析(ELISA)检测血清超敏肌钙蛋白(hs-cTnI)、肌酸激酶同工酶(CK-MB)水平,苏木素-伊红(HE)染色法观察大鼠心肌组织病理变化,透射电镜观察心肌自噬小体和自噬溶酶体变化,Western Blot法检测心肌组织PTEN诱导假定激酶1(PINK1)、E3泛素蛋白连接酶(Parkin)蛋白表达水平。【结果】与假手术组比较,模型组大鼠血肌酐(SCr)、尿素氮(BUN)、心脏质量指数、CK-MB、hs-cTnI升高(P<0.05),心脏病理损伤明显,自噬小体、自噬溶酶体减少,心肌组织PINK1、Parkin蛋白表达量降低(P<0.05);与模型组比较,大蒜素低、高剂量组大鼠SCr、BUN,心脏质量指数,CK-MB、hs-cTnI下降,心脏病理损伤程度减轻,自噬小体、自噬溶酶体增多,PINK1、Parkin蛋白表达量升高(P<0.05)。【结论】大蒜素可以减轻尿毒症大鼠心肌损伤,其机制可能与上调PINK1/Parkin介导的线粒体自噬有关。Objective To observe the therapeutic effect and mechanism of allicin on uremic-induced myocardial injury in rats.Methods Twenty-four rats were randomly divided into sham-operated group,model group,and low-,and high-dose allicin groups,with six rats in each group.Except for the sham-operated group,the uremic-induced myocardial injury model was constructed using the 5/6 nephrectomy method in all other groups of rats.After successful modeling,corresponding interventions were carried outed.At the end of the intervention,the renal function of rats was observed,the cardiac mass index was calculated,the levels of serum high-sensitive cardiac troponinⅠ(hs-cTnI)and creatine kinase isoenzyme(CK-MB)were detected by enzyme-linked immunosorbent assay(ELISA),the pathological changes of rat cardiac tissues were observed by hematoxylin-eosin(HE)staining,the changes of autophagosomes and autolysosomes were observed by transmission electron microscopy,and the protein expressions of PTEN-induced putative kinase 1(PINK1)and E3 ubiquitin protein ligase(Parkin)in myocardial tissues were detected by Western Blot.Results Compared with the sham-operated group,the serum creatinine(SCr),blood urine nitrogen(BUN),cardiac mass index,CK-MB and hs-cTnI in rats in the model group were elevated(P<0.05),the pathological damage of cardiac tissues were obvious,and the autophagosomes and autolysosomes were decreased,and PINK1 and Parkin protein expressions in myocardial tissues were decreased(P<0.05);compared with the model group,SCr,BUN,cardiac mass index,CK-MB and hs-cTnI in allicin low-and hogh-dose groups were decreased,the changes of pathological damage of cardiac tissues were relieved,the autophagosomes and autolysosomes were increased,and PINK1 and Parkin protein expressions in myocardial tissues were increased(P<0.05).Conclusion Allicin can reduce myocardial injury in uremic rats,and its mechanism may be related to the up-regulation of PINK1/Parkin-mediated mitochondrial autophagy.

关 键 词：大蒜素 尿毒症心肌损伤 线粒体自噬 PINK1 PARKIN 大鼠 

分 类 号：R285.5[医药卫生—中药学]