黄芪甲苷及人参皂苷Rg1对高脂大鼠心肌缺血再灌注损伤后心肌线粒体自噬的影响  

Effect of AstragalosideIV and Ginsenoside Rg1 on Autophagy of Myocardial Tissue Injury Induced by Ischemia-Reperfusion Injury in Hyperlipidemic Mice

作　　者：张东伟[1] 赵宏月 李全生[1] 杨关林[1] 闵冬雨[1] 宋囡 张会永[1] 贾连群 张哲[1] 曹慧敏 ZHANG Dongwei;ZHAO Hongyue;LI Quansheng;YANG Guanlin;MIN Dongyu;SONG Nan;ZHANG HuiyongJIA Lianqun;ZHANG Zhe;CAO Huimin(Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学附属医院,辽宁沈阳HOO32

出　　处：《中华中医药学刊》2020年第3期60-64,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：国家重点基础研究发展计划(973计划)(2013CB531704);国家自然科学基金(81603513);辽宁省科技厅项目(201602503);辽宁省教育厅创新团队(辽宁省教育厅高校科研基金)项目(LT201601).

摘　　要：目的研究黄芪甲苷(ASⅣ)及人参皂苷Rg1(Gin Rg1)对高脂大鼠心肌缺血再灌注损伤后心肌线粒体自噬的影响,并探讨其机制。方法采用高脂膳食喂养的方法复制高脂大鼠模型,再通过夹闭冠状动脉的方法复制心肌缺血再灌注大鼠(MI/R)模型,选取40只健康成年雄性SD大鼠随机分为假手术组(sham组)、高脂模型组(model组)、黄芪甲苷治疗组(ASⅣ组)、人参皂苷Rg1治疗组(Gin Rg1组)、黄芪甲苷+人参皂苷Rg1治疗组(合用组)5组,每组8只。通过可逆性左冠状动脉前降支结扎法建立心肌缺血再灌注模型,假手术组仅穿线不结扎。每组药物组大鼠给予相应的药物灌胃,每日3次,疗程1周,假手术组和高脂模型组给予等量的0.9%氯化钠注射液。治疗结束后,取腹主动脉血检测各组生化指标:CK、CK-MB、CHOL;酶联免疫法检测各组炎症指标:肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平;免疫印迹(Western Blot)检测低氧诱导因子1α(HIF1-α)、核呼吸因子1(NRF-1)及PINK1、Parkin蛋白的表达。结果与假手术组相比,模型组大鼠血清CK、CK-MB、CHOL水平、TNF-α水平、IL-6水平升高,差异有统计学意义(P<0.01或P<0.05);与模型组相比,药物组大鼠的CK、CK-MB、TNF-α、IL-6水平下降,差异具有统计学意义(P<0. 05);与模型组相比,药物组CHOL水平略有下降,但差异无统计学意义(P>0.05)。药物组与模型组相比,HIF1-α表达增强,NRF-1、PINK1、Parkin蛋白的表达下调。结论黄芪甲苷及人参皂苷Rg1能降低高脂大鼠心肌缺血再灌注的损伤,且两者合用作用增强。其作用机制可能与黄芪甲苷及人参皂苷Rg1降低炎症反应、抑制PINK1-Parkin介导的线粒体过度自噬相关。Objective The present study aimed to investigate the effect and mechanism of astragalosideⅣ and ginsenoside Rg1 on autophagy of myocardial tissue injury induced by ischemia-reperfusion injury(I/R) in hyperlipidemic mice.Methods Forty healthy adult male SD mice were fed by high-fat diet in order to replicate the hyperlipidemic mice model.They were randomly divided into 5 groups including sham operation group(sham group), hyperlipidemic mice model group(model group), astragalosideⅣ treatment group(ASⅣgroup), ginsenoside Rg1 treatment group(ginsenoside Rg1 group) and astragalosideⅣ+ginsenoside Rg1 treatment group(combined group) and 8 mice in each group.The myocardial ischemia reperfusion rat model(MI/R) was replicated by clipping the coronary arteryreversibly, mice in thesham group only were performed threading without ligation.Mice in the drug groups were given corresponding drugs by gavage for 3 times a day for 1 week,while mice in the sham group and model group were given the same amount of 0.9% NaCl1 week later,the biochemical indexes of CK, CK-MB and CHOL were determined in each group. The levels of the tumor necrosis factorα(TNF-α)and interleukin-6(IL-6) were determined by enzyme linked immunosorbent assay. The expression levels of autophagy related proteins PINK1,Parkin and hypoxia-inducible factor la(HIF1-α) were detected by Western Blot.Results Compared with the sham group, the serum levels of CK, CK-MB, CHOL,TNF-α and IL-6 in the model group were increasedstatistically(P<0.01 or P<0.05).Compared with the model group, the serum levels ofCK,CK-MB,TNF-αand IL-6 mice in the drug groups were decreasedstatistically(P<0. 05). CHOL levels were slightly lower in the drug groups than those in the model group, but the difference was not statistically significant(P>0.05).Compared with the model group, the expressions of HIF1-αwere enhanced and the expressions of NRF-1,PINK1 and Parkin proteins were down-regulated in the drug groups.Conclusion Astragaloside Ⅳ and ginsenoside Rg1 can reduce myocardial i

关 键 词：高脂大鼠 黄芪甲苷 人参皂苷RG1 缺血再灌注损伤 自噬 

分 类 号：R285.5[医药卫生—中药学]