牛磺酸对于心肌炎及其继发纤维化的抑制作用

 目的 研究牛磺酸(taurine,Tau) 对柯萨奇病毒B₃及多柔比星(ADR)所致心肌炎后心肌纤维化的抑制作用并探讨其机制。方法 ①以柯萨奇病毒B₃建立小鼠病毒性心肌炎模型,分为正常对照组、病毒性心肌炎模型组及Tau治疗组(1 000、500和250 mg·kg-1·d-1),测定小鼠血清中乳酸脱氢酶（LDH)、天冬氨酸氨基转移酶（AST）、肌酸激酶同工酶MB（CK-MB）的含量及超氧化物歧化酶（SOD）的活性,电镜观察心肌超微结构的变化。②以ADR建立大鼠心肌炎模型,将实验动物分为模型组及Tau 治疗组(400、200、100 mg·kg-1·d-1) ,检测大鼠血清中LDH、AST、肌酸激酶（CK）、丙二醛（MDA）的含量及SOD的活性变化;ELISA 法测定大鼠血清中转化生长因子β₁ (TGF-β₁ )及肿瘤坏死因子α(TNF-α)的含量;HE染色观察各组心肌组织的改变。 结果 ①柯萨奇病毒B₃可导致小鼠心肌细胞损伤,模型组血清中LDH、AST、CK-MB的含量增高、SOD的活性降低,而Tau各剂量治疗组均可降低LDH、AST、CK-MB的含量（P<0.05或P<0.01）,Tau治疗组(1 000、500 mg·kg-1·d-1)可增强SOD的活性（P<0.05或P<0.01）;电镜显示模型组肌节紊乱、断裂、溶解,肌丝部分溶解,肌膜破损,心肌细胞排列混乱,Tau治疗组心肌组织损伤程度得到改善。②大鼠心肌炎Tau (400、200 mg·kg-1·d-1)治疗组的LDH、AST 、CK及MDA的含量明显降低,SOD活性增强,Tau (400、200、100 mg·kg-1·d-1)治疗组TGF-β₁及TNF-α含量均降低,与模型组比较具有统计学差异（P<0.05或P<0.01）;HE 染色显示,ADR模型组心肌纤维增生,排列紊乱,肌浆肿胀,细胞内水肿,线粒体结构损害,Tau 明显减轻ADR所引起的心肌损伤。结论 Tau 可通过抗脂质过氧化作用,对柯萨奇病毒B₃、ADR所致心肌炎发挥保护作用,并抑制TGF-β₁及TNF-α的表达,降低ADR心肌炎继发的心肌纤维化的发生。

Inhibition Effect of Taurine on Myocarditis and Myocardial Fibrosis Followed by Myocarditis

OBJECTIVE To investigate the inhibition effect of taurine (Tau) on the myocarditis induced by Coxsackie virus and adriamycin, and myocardial fibrosis followed by myocarditis and its mechanism .METHODS ①The model of viral myocarditis was built by Coxsackie virus B₃ in mice, meanwhile, mice were treated with Tau 1 000,500 and 250 mg·kg-1·d-1 by gastrointestinal administration. The contents of lactate dehydrogenase (LDH), aspartate amino transferase （AST）,reatine kinase isozyme(CK-MB)and the activity of superoxide dismutase(SOD) in blood serum were assayed respectively. The changes of myocardial ultrastructure were observed by electronic microscope. ②The model of myocarditis in rats was built by intraperitoneal injection of adriamycin(ADR) for 2.5 mg·kg-1·week-1. Meanwhile, rats were treated with Tau 400,200 and 100 mg·kg-1·d-1 by gastrointestinal administration. The contents of LDH,AST,CK, malondialdehyde （MDA）and activity of SOD were measured. TGF-β₁ and TNF-α levels were determined by the ELISA.Histopathology changes were detected by HE staining. RESULTS ①Compared with model group, the contents of LDH,AST and CK-MB of blood serum were significantly reduced and the activity of SOD was markedly enhanced in Tau 1 000 and 500 mg·kg-1·d-1groups（P<0.05 or P<0.01）.The RESULTS of electron microscope showed that Tau relieved myocardial damage induced by Coxsackie virus B₃. ②Compared with model group, the contents of LDH, AST, CK, MDA were decreased in Tau groups (400, 200 mg·kg-1·d-1). The activity of SOD was increased and the contents of TGF-β₁,TNF-α were decreased（P<0.05 or P<0.01）.The cardiac myocytes were arranged disorder. Tau relieved the damages of myocardium caused by adriamycin.CONCLUSION Tau can inhibit the damages of myocardium caused by Coxsackie virus B₃ and adriamycin through antioxidation, inhibit myocardial fibrosis followed by myocarditis by inhibition the expressions of TGF-β₁ and TNF-α.