曲尼司特抑制病毒性心肌炎小鼠心肌纤维化的作用  

Tranilast inhibits myocardial fibrosis in mice with viral myocarditis

作　　者：文纯[1] 谢圭 曾萍[1] 黄林枫[1] 陈淳媛[1] 

机构地区：[1]中南大学湘雅三医院儿科,湖南长沙410013

出　　处：《中国当代儿科杂志》2016年第5期446-454,共9页Chinese Journal of Contemporary Pediatrics

基　　金：湖南省自然科学基金(13JJ3034)

摘　　要：目的探讨曲尼司特对病毒性心肌炎(VMC)小鼠心肌纤维化的作用。方法 72只BALB/C小鼠完全随机分为对照组、模型组和干预组(n=24),对照组小鼠腹腔内注射Eagle's培养液,模型组和干预组腹腔注射科萨奇病毒B3建立VMC模型,干预组建模后予曲尼司特灌胃(每日200 mg/kg),维持给药到取材前一天。分别在造模后7、14、28 d三个时间点每组各取8只小鼠心肌组织,行苏木精-伊红染色和Masson染色观察病理改变;甲苯胺蓝和硫瑾染色观察肥大细胞(MC)计数;RT-PCR及Western blot检测结缔组织生长因子(CTGF)、Ⅰ型胶原蛋白(ColⅠ)的m RNA及蛋白表达量;并分别对CTGF m RNA与MC计数和ColⅠm RNA的表达进行相关性分析。结果各时间点模型组心肌病理积分及胶原容积分数高于对照组,曲尼司特干预后降低(P<0.05)。模型组MC计数、CTGF和ColⅠm RNA及蛋白的表达高于对照组,曲尼司特干预后降低,但仍高于对照组(P<0.05)。模型组7 d、14 d时心肌MC计数与CTGF m RNA呈正相关(r=0.439,P=0.049);模型组7 d、14 d时心肌组织CTGF m RNA与ColⅠm RNA呈正相关(r=0.646,P=0.007),28 d时亦呈正相关(r=0.326,P=0.031)。结论曲尼司特可能通过抑制MC的聚集、降低CTGF和ColⅠ的表达,减轻VMC小鼠心肌纤维化效应。Objective To investigate the effect of tranilast on myocardial fibrosis in mice with viral myocarditis（VMC）.Methods Male balb/c mice（n=72）were randomly divided into control,VMC and tranilast groups（n=24 each）.In the VMC and tranilast groups,the mice were infected with Coxsackie virus B3（CVB3）to prepare VMC model,while the control group was treated with Eagle＇s medium.After modeling,the tranilast group was administrated with tranilast [200 mg/（kg.d）] until the day before sampling.On days 7,14 and 28 after CVB3 or Eagle＇s medium infection,heart specimens（n=8）were taken and examined after Toluidine blue staining and Nissl staining for counts of mast cells（MC）,hematoxylin-eosin staining for myocardial pathological changes,and Masson staining for myocardial fibrosis.The expression of CTGF and type I collagen（Col I）in the myocardial tissue was measured by RT-PCR and Western blot.The correlations of CTGF m RNA expression with MC counts and Col I expression were analyzed.Results The myocardial pathological changes and collagen volume fraction in the VMC group were significantly higher than in the control group at all three time points（P〈0.05）.Tranilast treatment significantly decreased the myocardial pathological changes and collagen volume fraction compared with the VMC group（P〈0.05）.The m RNA and protein expression of CTGF and Col I increased in the VMC group compared with the control group,and the increases were reduced with tranilast treatment（P〈0.05）.The number of MC was positively correlated to CTGF m RNA expression on the 7th day and 14 th day（r=0.439,P=0.049）in the VMC group.There were positive correlations between the m RNA expression of Col I and CTGF on the 7th day and 14 th day（r=0.646,P=0.007）and the 28 th day（r=0.326,P=0.031）.Conclusions Tranilast may inhibit the aggregation of MC and down-regulate the expression of CTGF,relieving myocardial fibrosis of mice with VMC.

关 键 词：曲尼司特 病毒性心肌炎 心肌纤维化 结缔组织生长因子 Ⅰ型胶原蛋白 小鼠 

分 类 号：R965[医药卫生—药理学]