摘要
目的探讨益脉颗粒对高脂大鼠心肌缺血再灌注损伤(MIRI)后线粒体动力学的影响。方法选取40只健康成年雄性SD大鼠随机分为假手术组、高脂模型组、益脉颗粒高剂量组、益脉颗粒中剂量组、益脉颗粒低剂量组5组,每组8只。采用高脂膳食喂养的方法复制高脂大鼠模型,再通过可逆性左冠状动脉前降支结扎法建立MIRI模型,假手术组仅穿线不结扎。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,通过Western Blot检测心肌细胞内线粒体分裂蛋白Drp1、Fis1与融合蛋白Mfn1、Mfn2、OPA1及线粒体生物合成关键调控因子PGC-1α的蛋白表达水平。结果与假手术组相比,模型组大鼠心肌OPA1、Mfn1、PGC-1α蛋白表达降低,Mfn2、Drp1、Fis1蛋白表达增加(P<0.01)或(P<0.05)。与模型组相比,益脉颗粒高、中剂量组大鼠心肌Drp1、Fis1蛋白表达降低,益脉颗粒低剂量组大鼠心肌Fis1蛋白表达降低(P<0.01)或(P<0.05);益脉颗粒高剂量组大鼠心肌Mfn2蛋白表达降低,Mfn1、OPA1蛋白表达升高,益脉颗粒中、低剂量组大鼠心肌Mfn1、OPA1蛋白表达升高(P<0.01)或(P<0.05),Mfn2蛋白表达有降低趋势;益脉颗粒高、中、低剂量组大鼠心肌PGC-1α蛋白相对表达量显著增强(P<0.01)或(P<0.05)。药物组大鼠心脏PGC-1α、OPA1、Mfn1蛋白相对表达量显著增强(P<0.01)或(P<0.05),Mfn2、Drp1、Fis1蛋白表达下降(P<0.01)或(P<0.05)。结论益脉颗粒可能通过调控线粒体融合、裂解、合成等相关蛋白,调控线粒体动态平衡进而对高脂血症大鼠心肌缺血再灌注损伤起保护作用。
Objective To investigate the effects of Yimai Granule(益脉颗粒)on myocardial dynamics after myocardial ischemia reperfusion injury(MIRI)in hyperlipidemia rats.Methods Forty healthy adult male SD rats were randomly divided into 5 groups including the sham operation group,the model group,the high,medium and low dose groups of Yimai Granule,with 8 rats in each group.The high-fat diet was used to replicate the hyperlipidemia rat model.The rat model of MIRI was replicated by clamping the coronary artery.The sham operation groupwas only threaded without ligation.Rats in the high,medium and low dose groups of Yimai Granule were given different concentrations of Yimai Granuleby gavage 3 times a day for 1 week.The sham operation group and the model group were given the same amount of 0.9%sodium chloride.After the treatment was completed,Western blot analysis was used to detect the relative expression levels of mitochondrial fission proteins(Drp1,Fis1 protein),mitochondrialfusion proteins(Mfn1,Mfn2,OPA1 proteins)and mitochondrial biosynthesis related proteins(PGC-1αprotein)in rats cardiomyocytes.Results Compared with the sham operated rats,the expression levels of OPA1,Mfn1 and PGC-1αprotein in the model group were decreased and the expression levels of Mfn2,Drp1 and Fis1 protein were increased(P<0.01).Compared with the model group,the expression levels of Drp1 and Fis1 protein in the high and medium dose groups of Yimai Granulewere decreased(P<0.01,P<0.05).The expression level of Fis1 protein in the low dose group was decreased(P<0.01,P<0.05).The expression level of Mfn2 protein was decreased and the expression levels of Mfn1 and OPA1 protein were increased in the high dose group of Yimai Granule.The expression levels of Mfn1 and OPA1 protein in the medium and low dose groups of Yimai Granule were increased(P<0.01,P<0.05),and the expression level of Mfn2 protein was decreased,which had no statistical difference.The relative expression level of PGC-1αprotein in the high,medium and low dose groups of Yimai Granule were significantly increased(P<0.01,P<0.05).Conclusion Yimai Granule may regulate the mitochondrial dynamic balance by regulating mitochondrial fusion protein,fission protein and mitochondrial synthesis related proteinto protect the myocardium of hyperlipidemia combined with MIRI rats.
作者
张东伟
赵宏月
杨关林
闵冬雨
宋囡
张会永
贾连群
张哲
曹慧敏
ZHANG Dongwei;ZHAO Hongyue;YANG Guanlin;MIN Dongyu;SONG Nan;ZHANG Huiyong;JIA Lianqun;ZHANG Zhe;CAO Huimin(The Affiliated Hospital of Liaoning University of TCM,Shenyang 110032,Liaoning,China;Liaoning University of TCM,Shenyang 110032,Liaoning,China)
出处
《辽宁中医杂志》
CAS
2021年第4期187-191,共5页
Liaoning Journal of Traditional Chinese Medicine
基金
国家重点基础研究发展计划(“973”计划)(2013CB531704)
沈阳市科技计划项目(19-112-4-060)
第一批国家中医药骨干创新人才基金(辽中医药医疗字[2019]68号)
辽宁省教育厅创新团队(辽宁省教育厅高校科研基金)(LT201601)。
关键词
益脉颗粒
高脂血症
心肌缺血再灌注损伤
线粒体动力学
Yimai Granule(益脉颗粒)
hyperlipidemia
myocardial ischemia reperfusion injury
mitochondrial dynamics
