曲尼司特对病毒性心肌炎小鼠心肌纤维化的作用  

Effect of tranilast on myocardial fibrosis in mice with viral myocarditis

作　　者：黄林枫[1] 文纯[1] 谢圭 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》2014年第11期1154-1161,共8页Chinese Journal of Contemporary Pediatrics

基　　金：湖南省自然科学基金(13JJ3034);中南大学研究生创新课题(2013zzts340);中南大学湘雅三医院重点学科建设基金

摘　　要：目的探讨曲尼司特在病毒性心肌炎心肌纤维化中的作用。方法 72只BALB/C小鼠随机分为对照组、模型组和干预组(n=24)。模型组和干预组小鼠感染柯萨奇病毒B3建立病毒性心肌炎模型,其中干预组小鼠造模后即用曲尼司特(200 mg/kg)灌胃给药直到取材前一天;对照组和模型组小鼠予等量生理盐水灌胃。造模后第7、14、28天取各组8只小鼠心肌组织,甲苯胺蓝染色、硫堇染色检测心脏肥大细胞数目,苏木精-伊红染色观察心肌组织病理学变化,Masson三色染色观察心肌纤维化,RT-PCR、免疫组化检测骨桥蛋白(OPN)、转化生长因子-β1(TGF-β1)的mRNA及蛋白表达,并对OPN mRNA与肥大细胞数目作相关性分析。结果模型组和干预组小鼠心肌组织OPN mRNA及蛋白的表达于第7天达最高,第14天次之,第28天最低;TGF-β1 mRNA及蛋白的表达第7天升高,第14天达高峰,第28天较前稍下降;干预组小鼠心肌组织TGF-β1、OPN mRNA及蛋白在各时间点的表达均低于模型组(均P<0.05),但仍高于对照组(均P<0.05)。肥大细胞的数目与OPN的表达呈正相关。结论曲尼司特可能通过减少肥大细胞数,抑制TGF-β1及OPN表达,在抗心肌纤维化过程中起重要作用。Objective To study the role of tranilast in the pathogenesis of myocardiac ifbrosis in viral myocarditis. Methods Seventy-two BALB/C mice were randomly divided into control, model and intervention groups （n=24 each）. Mice in the model and intervention groups were infected with Coxsackievirus B3 to induce viral myocarditis. The intervention group was given with tranilast （200 mg/kg） by gavage until sacriifce for sampling, while the other two groups were administered with the same volume of normal saline. Cardiac tissues were obtained from 8 mice on 7, 14 and 28 days after modeling. The mast cell number was observed by toluidine blue staining and thionine staining. The cardiac tissues were stained with hematoxylin and eosin as well as masson trichrome to observe the pathological changes in cardiac tissues. The mRNA and protein expression of osteopontin and transforming growth factor-β1 was measured by RT-PCR and immunohistochemistry respectively. Results In the model group, the mRNA and protein expression of osteopontin reached the highest level on the 7th day, decreasing from the 14th day, and became to the least on the 28th day;while the expression of TGF-β1 increased from the 7th day, reaching a peak on the 14th day, and decreased slightly on the 28th day. The mRNA and protein expression of TGF-β1 and OPN was lower in the intervention group than the model group （P〈0.05）, but higher than the control group （P〈0.05）. The expression of OPN mRNA was positively correlated to the number of mast cells. Conclusions Tranilast can reduce myocardial ifbrosis by decreasing the number of mast cells, inhibiting the expression of TGF-β1 and OPN.

关 键 词：曲尼司特 肥大细胞 骨桥蛋白 心肌纤维化 小鼠 

分 类 号：R725.4[医药卫生—儿科]