百令胶囊对病毒性心肌炎小鼠心肌纤维化及TGF-β1-MAPK/ERK通路的影响  

Effect of Bailing capsule on myocardial fibrosis and TGF-β1-MAPK/ERK pathway of viral myocarditis rats

作　　者：吴岚[1] 吕欣桐[1] 张春艳[1] 孙景辉[1] 王朝霞 

机构地区：[1]吉林大学第一医院儿科,长春130021 [2]深圳市儿童医院,深圳518038

出　　处：《中国免疫学杂志》2017年第10期1493-1497,共5页Chinese Journal of Immunology

基　　金：吉林省科技厅重点项目资助课题(20140204041)

摘　　要：目的:探讨百令胶囊(BL)对病毒性心肌炎(VMC)小鼠心肌纤维化及TGF-β1-MAPK/ERK通路的影响。方法:200只健康雄性BALB/c小鼠中的180只采用间断多次腹腔注射组织培养半数感染量(TCID50)100 TCID50/0.1 ml的柯萨奇病毒B3(CVB3)病毒稀释液,建立VMC心肌纤维化模型,另外20只注射不含病毒的Eagle's液作为正常对照组。两个月后模型制作成功。存活的小鼠随机分为4组,模型组、BL高、中、低剂量组。分别给予不同剂量BL进行治疗,每日灌胃给药一次,60 d后结束。心脏超声检测左室舒张末期内径(LVEDd)和左室收缩末期内径(LVEDs),并计算左室射血分数缩短率(FS);采用免疫组化法检测心肌组织Ⅰ型胶原、Ⅲ型胶原;Masson染色计算心肌胶原容积分数(CVF);测定采用半定量Western blot法检测心肌TGFβ1及p-ERK1/2蛋白的表达。结果:(1)与对照组比较,模型组小鼠心肌CVF、Ⅰ型、Ⅲ型胶原明显增高,心脏LVEDd,LVEDs升高,FS下降,差异有统计学意义(P<0.05)。(2)与对照组比较,模型组心肌TGF-β1及p-ERK1/2蛋白表达升高,差异有统计学意义(P<0.05)。(3)与模型组比较,BL大、中剂量组CVF、Ⅰ型、Ⅲ型胶原下降,心脏LVEDd,LVEDs下降,FS升高,差异有统计学意义(P<0.05)。(4)与模型组比较,BL大剂量组心肌TGF-β1及p-ERK1/2蛋白表达下降,差异有统计学意义(P<0.05)结论:(1)百令胶囊可以改善病毒性心肌炎小鼠减轻心肌纤维化,改善心功能。(2)在病毒性心肌炎中,TGF-β1-MAPK/ERK通路激活可能起促心肌纤维化作用。(3)百令胶囊抗心肌纤维化作用机制可能是通过抑制TGF-β1-MAPK/ERK通路的活化实现的。Objective： To investigate the effect of Bailing capsule on myocardial fibrosis in mice with viral myocarditis（ VMC）and TGF-β1-MAPK/ERK pathway. Methods： Male BALB/c mice（ n = 200） were randomly divided into model group（ n = 180） and control group（ n = 20）. The model group mice were infected with Coxsackie virus B3 to prepare VMC myocardial fibrosis. The control group mice were injected with Eagle＇s MEM without virus. The model was successful after two months. The survival mice were randomly divided into model group and high,middle and low dose of Bailing capsule was administered consecutively for sixty days,once a day,Cardiac ultrasound was used to test LVEDd,LVEDs,then calculate FS. The expression of type Ⅰ collagen and type Ⅲ collagen in all the mice myocardial tissue was detected by immunohistochemical methods. Masson staining for myocardial fibrosis was used to calculate the collagen volume fraction（ CVF）. Western blot was used to detect the protein expression of TGF-β1 and p-ERK1/2. Results：（1）Compared with the control group,the CVF,type Ⅰ collagen and type Ⅲ collagen obviously increased,LVEDd,LVEDs increased,FS decreased,which had statistically significance（ P〈0. 05）.（2）Compared with the control group,the model group of mice had a statistically significantly higher expression of TGF-β1 and p-ERK1/2（ P〈0. 05）.（3）Compared with the model group,the expression of CVF,type Ⅰcollagen and type Ⅲ collagen of high and middle dose of Bailing capsule was significantly lower,LVEDd,LVEDs decreased,while FS increased（ P〈0. 05）.（4）Compared with the model group,the high dose of Bailing capsule group of mice had a statistically significantly lower expression of TGF-β1 and p-ERK1/2（ P〈0. 05）. Conclusion：（1） Bailing capsule can prevent myocardial fibrosis of mice with VMC.（2）The activation of TGF-β1-MAPK/ERK pathway may can promote myocardial fibrosis in VMC.（3）Bailing capsule could prevent myocardial fibrosis,which may be relate

关 键 词：病毒性心肌炎 心肌纤维化 信号通路 百令胶囊 

分 类 号：R72[医药卫生—儿科]