中风活心软胶囊通过靶向微小RNA-126诱导缺氧诱导因子-1α/促凋亡调节蛋白BNIP3信号通路促进自噬减轻脑缺血再灌注损伤大鼠神经损伤的作用机制研究  

Study on mechanism of hypoxia-inducing factor-1α/proapoptotic regulatory protein BNIP3 signaling pathway induced by Zhongfeng Huoxin soft capsule to promote autophagy and reduce nerve injury in rats with cerebral ischemia reperfusion injury by targeting micro RNA-126

作　　者：许良葵[1] 黄海潮[2] 聂阳[1] XU Liangkui;HUANG Haichao;NIE Yang(School of Pharmaceutical Engineering,Guangdong Vocational College of Food and Drug,Guangzhou,Guangdong,510520,China;Experimental Training Center,Guangdong Vocational College of Food and Drug,Guangzhou,Guangdong,510520,China)

机构地区：[1]广东食品药品职业学院制药工程学院,广东广州510520 [2]广东食品药品职业学院实验实训中心,广东广州510520

出　　处：《当代医学》2024年第11期1-6,共6页Contemporary Medicine

基　　金：2021年度广东省中医药局中医药科研项目(20202164)。

摘　　要：目的探讨中风活心软胶囊通过靶向微小RNA(miRNA)-126诱导缺氧诱导因子-1α(HIF-1α)/促凋亡调节蛋白BNIP3信号通路促进自噬减轻脑缺血再灌注损伤大鼠神经损伤的作用机制。方法选取30只无特定病原体(SPF)级雄性SD大鼠,随机分为空白组、模型组与治疗组,每组10只。采用Zea Longa法建立右侧大脑中动脉缺血(MCAO)大鼠模型。治疗组给予中风活心软胶囊。采用改良神经功能损害评分(mNSS)评估大鼠神经功能缺损情况,透射电镜观察缺血半暗区皮质神经元及自噬囊泡超微结构,蛋白质免疫印迹(WB)法和实时荧光定量聚合酶链式反应(RT-qPCR)法分别检测缺血半暗区皮质雷帕霉素靶蛋白(mTOR)、HIF-1α蛋白及其mRNA和miR-126的表达水平。结果模型组、治疗组mNSS评分均高于对照组,但治疗组低于模型组,差异有统计学意义(P<0.05)。模型组、治疗组缺血半暗区皮质mTOR、HIF-1α蛋白表达水平均高于对照组,但治疗组低于模型组,差异有统计学意义(P<0.05)。模型组、治疗组缺血半暗区皮质mTOR、HIF-1αmRNA表达水平均高于对照组,miR-126表达水平低于对照组,但治疗组mTOR、HIF-1αmRNA表达水平低于模型组,miR-126表达水平高于模型组,差异有统计学意义(P<0.05)。治疗组缺血半暗区皮质神经元及电镜下自噬囊泡数量明显增加,细胞结构损坏减轻。结论中风活心软胶囊可显著提高脑缺血大鼠缺血半暗区皮质mTOR、HIF-1α因子表达,其作用机制可能是通过激活miR-126表达进而靶向调控mTOR/HIF-1α信号通路,促进自噬,从而发挥其脑保护效应。Objective To investigate the mechanism of hypoxia-inducing factor-1α(HIF-1α)/pro-apoptotic regulatory protein BNIP3 signaling pathway induced by Zhongfeng Huoxin soft capsule to promote autophagy and reduce nerve injury in rats with cerebral ischemia reperfusion injury by targeting micro RNA(miRNA)-126.Methods 30 male SD rats of specific pathogen free(SPF)grade were selected and randomly divided into the blank group,model group and the treatment group,with 10 rats in each group.The right middle cerebral artery occlusion(MCAO)rat model was established by Zea Longa method.The treatment group was given Zhongfeng Huoxin soft capsules.The modified neurological severity score(mNSS)was used to evaluate the neurological deficits of rats,the ultrastructure of neurons and autophagic vesicles in the ischemic penumbra cortex was observed by transmission electron microscopy,the expression levels of mammalian target of Rapamycin(mTOR),HIF-1αprotein and mRNA and miR-126 in the ischemic penumbra cortex were detected by Western blot(WB)and real time quantitative PCR(RT-qPCR),respectively.Results The mNSS scores in the model group and the treatment group were higher than those in the control group,but the treatment group was lower than the model group,and the differences were statistically significant(P<0.05).The expression levels of mTOR and HIF-1αprotein in the ischemic penumbra cortex in the model group and the treatment group were higher than those in the control group,but the treatment group was lower than the model group,and the differences were statistically significant(P<0.05).The expression levels of mTOR and HIF-1αmRNA in the ischemic area of the model group and the treatment group were higher than those in the control group,and the expression level of miR-126 was lower than that in the control group,but the expression levels of mTOR and HIF-1αmRNA in the treatment group were lower than those in the model group,and the expression level of miR-126 was higher than that in the model group,the differences were statisti

关 键 词：中风活心软胶囊 微小RNA-126 诱导因子-1α/促凋亡调节蛋白BNIP3信号通路 自噬 脑缺血再灌注损伤 神经损伤 

分 类 号：R285[医药卫生—中药学]