心肌炎小鼠心肌纤维化与心脏上皮/内皮间充质转化的关系

目的: 探讨心脏上皮/内皮间充质转化(EMT/EndMT)与病毒性心肌炎心肌纤维化的关系。方法: 40只BALB/c 小鼠随机分为2组,分别为对照组(n=16)和心肌炎组(n=24)。2组小鼠每周1次分别腹腔注射无病毒培养液或柯萨奇病毒B3(CVB3);于第7 d后随机处死2组小鼠各8只,30 d后处死其余存活小鼠。以苦味酸天狼星红染色检测小鼠心脏胶原容积分数(CVF),ELISA法检测血清胶原前肽的含量变化,以实时RT-PCR法和Western blotting方法检测小鼠心脏中EMT/EndMT蛋白组包括启动因子转化生长因子β₁(TGF-β₁)和Wnt1、转录因子Twist1、上皮细胞标志物上皮细胞钙黏素(E-cadherin)、内皮细胞表面标志血管内皮钙黏素(VE-cadherin)、间充质蛋白如成纤维细胞特异蛋白(FSP-1)和α-平滑肌肌动蛋白(α-SMA)等的基因和蛋白表达情况。结果: 急性病毒性心肌炎时,出现EMT/EndMT现象,其特征为VE-cadherin和E-cadherin丢失,FSP-1和α-SMA表达上调,启动因子TGF-β₁和Wnt1表达增高,转录因子Twist1表达增加,胶原合成增多;慢性期未发现上皮/内皮细胞表型丢失,间充质标志蛋白仍表达上调,胶原合成增多,TGF-β₁、Twist1和Wnt1表达依然增加。结论: EMT/EndMT参与了急性病毒性心肌炎心肌纤维化的形成,慢性期未发现EMT/EndMT参与心肌纤维化。

Relationship between myocardial fibrosis and epithelial/endothelial to mesenchymal transition in myocarditis mice

AIM: To investigate the relationship between epithelial/endothelial to mesenchymal transition(EMT/EndMT) and myocardial fibrosis in viral myocarditis.METHODS: Forty BALB/c mice were randomized to control group(n=16,intraperitoneally injected with virus-free vehicle weekly) and viral myocarditis group n=24, intraperitoneally injected with coxsackievirus B3(CVB3) weekly].Eight mice in each group were sacrificed on day 7 and the remaining survived mice were sacrificed on day 30 after inoculation.The cardiac c...