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 ischemia reperfusion injury in hyperlipidemic mice, and their combined effect was enhanced.The mechanism may be related to decreased inflammatory response and inhibition of excessive autophagy of mitochondria mediated by PINK1-Parkin pathway.
作者
张东伟
赵宏月
李全生
杨关林
闵冬雨
宋囡
张会永
贾连群
张哲
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)
出处
《中华中医药学刊》
CAS
北大核心
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).
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
hyperlipidemic mice
astragalosideⅣ
ginsenoside Rg1
ischemia-reperfusion injury
autophagy
