黄芪皂苷对病毒性心肌炎大鼠PI3K/AKT/mTOR信号通路和心肌细胞凋亡的影响  

Effects of saponins of astragalus on PI3K/AKT/mTOR signaling pathway and cardiomyocytes apoptosis in rats with viral myocarditis

作　　者：郑恒 张聪子[2] 徐金军[2] 章登政 甘露珍[2] 饶志威[2] ZHENG Heng;ZHANG Cong-zi;XU Jin-jun;ZHANG Deng-zheng;GAN Lu-zhen;RAO Zhi-wei(The First Affiliated Hospital of Hubei University of Science and Technology,Xianning Central Hospital,Xianning,Hubei 437100,China)

机构地区：[1]咸宁市中心医院,湖北科技学院附属第一医院心血管内科,湖北咸宁437100 [2]咸宁市中心医院,湖北科技学院附属第一医院药学部,湖北咸宁437100

出　　处：《中华医院感染学杂志》2022年第23期3521-3526,共6页Chinese Journal of Nosocomiology

基　　金：湖北省自然科学基金面上项目(2020CFB868);咸宁市中心医院院内基金项目(2018XYTS002)。

摘　　要：目的分析黄芪皂苷(SA)对病毒性心肌炎(VMC)大鼠磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素靶蛋白(mTOR)信号通路和心肌细胞凋亡的影响。方法制备VMC大鼠模型,随机分成正常组、模型组、SA低(40 mg/kg)、中(80 mg/kg)、高剂量(160 mg/kg)组,每组15只,造模成功后灌胃给药,连续15 d。超声心动图检测大鼠心功能。HE染色检测大鼠心肌组织病理变化。实时荧光定量聚合酶链反应(RT-PCR)检测柯萨奇B3病毒(CVB3)mRNA表达。生化仪检测血清心肌酶含量。酶联免疫吸附法检测大鼠血清炎症因子。蛋白免疫印迹检测蛋白。结果经SA干预可改善VMC大鼠心肌病理损伤,降低CVB3病毒表达量,提高短轴缩短率(LVFS)和左室射血分数(LVEF)水平,降低左室舒张末内径(LVEDd)和左室收缩末内径(LVESd)水平;减少血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)和肌钙蛋白I(cTnI)水平;降低肿瘤坏死因子(TNF-α)、干扰素γ(IFN-γ)、白细胞介素-7(IL-7)和白细胞介素-6(IL-6)水平;下调大鼠心肌组织中磷酸化磷酸肌醇3激酶(p-PI3K)/PI3K、磷酸化蛋白激酶B(p-AKT)/AKT、磷酸化雷帕霉素靶蛋白(p-mTOR)/mTOR、Bcl-2相关X蛋白(Bax)/B淋巴细胞瘤-2基因(Bcl-2)比值。结论SA可抑制PI3K/AKT/mTOR信号通路激活降低血清心肌酶、炎症因子水平,抑制CVB3基因复制,改善心肌损伤,增强心功能,抑制心肌细胞凋亡。OBJECTIVE To analyze the effects of saponins of astragalus(SA)on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signaling pathway and cardiomyocytes apoptosis in rats with viral myocarditis(VMC).METHODS The models of viral myocarditis(VMC)rats were prepared,and 75 rats were randomly divided into the normal group,model group,low-dose(40 mg/kg)group,medium-dose(80 mg/kg)group and high-dose(160 mg/kg)group,15 cases in each group.After successful modeling,rats were given intragastric administration for consecutive 15 days.The cardiac function of rats was tested by echocardiography.The pathological changes of myocardial tissues were detected by HE staining.The expression of Coxsackie virus B3(CVB3)mRNA was detected by RT-PCR.Serum content of myocardial enzyme was detected by biochemical analyzer.The levels of serum inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA).The proteins related to PI3K/AKT/mTOR signaling pathway were detected by Western Blot.RESULTS SA intervention could alleviate pathological damage of myocardial tissues in VMC rats,reduce CVB3 load level,increase levels of left ventricular fraction shortening(LVFS)and left ventricular ejection fraction(LVEF),shorten left ventricular end-diastolic diameter(LVEDd)and left ventricle end-systolic diameter(LVESd),decrease the levels of serum creatine kinase(CK),creatine kinase MB(CK-MB),cardiac troponin I(cTnI),serum tumor necrosis factorα(TNF-α),interferonγ(IFN-γ),interleukin-7(IL-7)and interleukin-6(IL-6),and down-regulate ratios of phosphorylated phosphoinositide 3-kinase(p-PI3K)/PI3K,phosphorylated protein kinase B(p-AKT)/AKT,phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR,and Bcl-2 associated X protein(Bax)/B lymphocytoma-2 gene(Bcl-2)in myocardial tissues.CONCLUSION SA can reduce levels of serum myocardial enzymes and inflammatory factors by inhibiting the activation of PI3K/AKT/mTOR signaling pathway,inhibit CVB3 gene replication,so as to improve myocardial injury,enhan

关 键 词：黄芪皂苷 病毒性心肌炎 磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白 信号通路 凋亡 

分 类 号：R542.21[医药卫生—心血管疾病]