Calpastatin减轻病毒性心肌炎心脏炎症损伤的作用  

Effects of Calpastatin on Cardiac Inflammatory Injury in CVB3-Induced Viral Myocarditis

作　　者：虞莹 石卉 虞勇[2] 陈瑞珍[2] YU Ying;SHI Hui;YU Yong;CHEN Rui-zhen(Department of General Practice,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Shanghai Institute of Cardiovascular Diseases,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院全科医学科,上海市200032 [2]复旦大学附属中山医院上海市心血管病研究所,上海市200032

出　　处：《中国分子心脏病学杂志》2019年第2期2848-2852,共5页Molecular Cardiology of China

基　　金：国家自然科学基金青年项目(81600294)国家自然科学基金面上项目(31570904)

摘　　要：目的探讨钙蛋白酶抑制蛋白(calpastatin)对柯萨奇B组病毒3型(coxsackievirus B3, CVB3)诱导的病毒性心肌炎小鼠心脏炎症损伤的作用。方法取全身过表达calpastatin的转基因小鼠(Tg-CAST)及野生型小鼠(WT)腹腔注射CVB3,感染病毒7d后建立病毒性心肌炎模型。分为对照组、Tg-CAST组、WT病毒性心肌炎组、Tg-CAST病毒性心肌炎组。留取小鼠心肌、血清及脾脏组织标本,分别行组织病理学检查以及炎症损伤相关因子检测。结果①WT病毒性心肌炎小鼠心肌组织中炎症浸润面积、病毒包膜蛋白VP-I及血清cTnI水平均明显高于对照组(P<0.001)。与WT病毒性心肌炎小鼠相比,Tg-CAST病毒性心肌炎小鼠心肌炎症浸润面积、VP-1及cTnI水平均明显降低(P<0.05)。②WT病毒性心肌炎小鼠心肌、脾脏与血清中炎症因子HMGB1、TNF-α、IL-17水平及心肌β-NF-κB表达显著升高(P<0.01),而Tg-CAST病毒性心肌炎小鼠相应指标均明显低于WT病毒性心肌炎小鼠(P<0.05)。结论 calpastatin可能通过抑制NF-κB通路活化降低病毒性心肌炎小鼠HMGB1、TNF-α、IL-17水平,进而改善心脏炎症损伤。Objective To investigate roles of calpastatin in the pathogenesis of coxsackievirus B3(CVB3)-induced viral myocarditis(VMC).Methods Transgenic mice overexpressing calpastatin(Tg-CAST) and wild type(WT) mice were utilized to establish the VMC model via intraperitoneal injection of CVB3 respectively. Mice were randomly divided into 4 groups: control group, Tg-CAST group, WT VMC group and Tg-CAST VMC group. Mice were sacrificed 7 days after infection, and heart, spleen and serum samples were harvested. Tissue sections were HEstained and histopathological examinations were proceeded, while levels of the inflammatory factors of HMGB1, TNF-a, IL-17 and p-NF-κB were observed and analyzed. Results Comparing with the control group, myocardium inflammatory area and the levels of VP-1 and cTnI were significantly elevated in WT VMC group, while there were significant reductions comparing with Tg-CAST VMC group respectively. The levels of HMGB1, TNF-a and IL-17 in myocardium, serum and spleen and the expression of p-NF-κβ in myocardium were significantly up-regulated in WT VMC group, which were attenuated in Tg-CAST VMC group. Conclusions Calpastatin overexpression alleviated CVB3-induced VMC via decreasing HMGB1, TNF-a and IL-17, which might be associated with the activation of NF-κβ pathway.

关 键 词：钙蛋白酶抑制蛋白 炎症 核因子κβ 

分 类 号：R542.21[医药卫生—心血管疾病]