重楼皂苷Ⅰ对柯萨奇病毒B3诱导的病毒性心肌炎小鼠心肌的保护作用及其机制  

Protective effect of polyphyllin Ⅰ on myocardium in mice with viral myocarditis induced by coxsackievirus B3

作　　者：江振涛 魏读辉 马小峰[1] 李招兵[1] JIANG Zhen-tao;WEI Du-hui;MA Xiao-feng;LI Zhao-bing(Department of Cardiovascular Medicine,Nanhua Hospital Affiliated to Nanhua University,Hengyang 421002,China)

机构地区：[1]南华大学附属南华医院心血管内科,湖南衡阳421002

出　　处：《中国病理生理杂志》2021年第11期1986-1991,共6页Chinese Journal of Pathophysiology

基　　金：湖南省卫生健康委2020年度科研立项课题(No.20201905)。

摘　　要：目的:探讨重楼皂苷Ⅰ(PPI)对柯萨奇病毒B3(CVB3)诱导的病毒性心肌炎(VMC)小鼠心肌的保护作用及其可能机制。方法:将75只BALB/c小鼠随机分成正常对照组(control组)、VMC模型组(VMC组)、阳性药物利巴韦林(RBV,0.02 g·kg^(−1)·d^(−1))组、低剂量(75 mg·kg^(−1)·d^(−1))PPI(L-PPI)组和高剂量(300 mg·kg^(−1)·d^(−1))PPI(H-PPI)组,每组15只。通过腹腔注射CVB3建立VMC小鼠模型,造模2 h后腹腔注射给药,每天1次,连续1周。HE染色观察小鼠心肌组织损伤情况;ELISA法检测血清中心肌损伤标志物心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)和肌红蛋白(Mb)水平,以及心肌组织中炎症因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和IL-1β含量;RT-qPCR检测心肌组织中CVB3 mRNA表达量;Western blot检测心肌组织中凋亡相关蛋白cleaved caspase-3、Bax和Bcl-2,以及NF-κB信号通路相关蛋白水平。结果:与control组比较,VMC小鼠心肌组织损伤严重,血清中cTnI、CK-MB和Mb含量,心肌组织中CVB3 mRNA表达量,IL-6、TNF-α和IL-1β含量,以及cleaved-caspase-3、Bax、p-IκBα(Ser32)和p-NF-κB(Ser536)蛋白水平均显著上升(P<0.01),Bcl-2蛋白表达水平显著降低(P<0.01);与VMC组比较,H-PPI和RBV组心肌组织损伤程度减轻,血清中cTnI、CK-MB和Mb含量,心肌组织中CVB3 mRNA表达量,IL-6、TNF-α和IL-1β含量,以及cleaved caspase-3、Bax、p-IκBα(Ser32)和p-NF-κB(Ser536)蛋白表达水平均显著下降(P<0.01),Bcl-2蛋白表达水平显著上升(P<0.01),而L-PPI组相关指标均无显著变化(P>0.05)。结论:PPI可能通过抑制NF-κB信号通路激活对VMC小鼠心肌组织起到保护作用。AIM:To investigate the protective effect of polyphyllin I(PPI)on the myocardium in mice with vi-ral myocarditis(VMC)induced by coxsackievirus B3(CVB3)and its possible mechanism.METHODS:BALB/c mice(n=75)were randomly divided into normal control(control)group,VMC model group(VMC)group,positive drug ribavi-rin(RBV,0.02 g·kg^(−1)·d^(−1))group,low-dose(75 mg·kg^(−1)·d^(−1))PPI(L-PPI)group and high-dose(300 mg·kg^(−1)·d^(−1))PPI(H-PPI)group,with 15 mice in each group.The VMC mouse model was established by intraperitoneal injection of CVB3.The mice were immediately injected with the corresponding drug intraperitoneally once a day for 1 week 2 h after modeling.The damage of myocardial tissue was observed by HE staining.The serum levels of myocardial injury markers cardiac troponin I(cTnI),creatine kinase-MB(CK-MB)and myoglobin(Mb),and the levels of inflammatory factors in-terleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1βin myocardial tissues were mrasured by ELISA.The mRNA expression of CVB3 in myocardial tissue was detected by RT-qPCR.The protein levels of apoptosis-related mole-cules cleaved caspase-3,Bax and Bcl-2,and NF-κB signaling pathway-related molecules in myocardial tissues were deter-mined by Western blot.RESULTS:Compared with control group,severe myocardial damage was observed in VMC group,and the serum levels of cTnI,CK-MB and Mb,the mRNA expression of CVB3,the levels of IL-6,TNF-αand IL-1β,and the protein levels of cleaved caspase-3,Bax,p-IκBα(Ser32)and β-NF-κB(Ser536)in myocardial tissues were significantly increased(P<0.01),while the protein expression level of Bcl-2 was significantly decreased(P<0.01).Com-pared with VMC group,the myocardial injury in H-PPI group and RBV group was attenuated,and the serum levels of cTnI,CK-MB and Mb,the mRNA expression of CVB3,the levels of IL-6,TNF-αand IL-1β,and the protein levels of cleaved caspase-3,Bax,p-IκBα(Ser32)and p-NF-κB(Ser536)in myocardial tissues were significantly decreased(P<0.01),while the protein expression level

关 键 词：重楼皂苷Ⅰ 柯萨奇病毒B3 病毒性心肌炎 NF-ΚB信号通路 细胞凋亡 

分 类 号：R542.21[医药卫生—心血管疾病] R363.2[医药卫生—内科学]