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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(1000、500和250mg·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、100mg·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(1000、500mg·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、200mg·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、100mg·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。
Objective To investigate the inhibitory effect of taurine (Tau) on myocardial fibrosis induced by coxsackievirus B3 and doxorubicin (ADR) and its possible mechanism. Methods ① The mouse models of viral myocarditis were established by coxsackievirus B3 and divided into normal control group, viral myocarditis model group and Tau treatment group (1000, 500 and 250 mg · kg-1.d-1) Serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase MB (CK-MB) content and superoxide dismutase (SOD) activity, electron microscopy myocardial Changes in ultrastructure. ② The model of myocarditis in rats was established by ADR. The experimental animals were divided into model group and Tau treatment group (400, 200, 100 mg · kg-1.d-1). Serum LDH, AST, creatine kinase ), Malondialdehyde (MDA) and the activity of SOD. The contents of TGF-β1 and TNF-α in the serum of the rats were determined by ELISA. Changes in myocardial tissue. Results ① Coxsackie B3 could induce cardiomyocyte injury in mice. The content of LDH, AST, CK-MB and the activity of SOD decreased in the model group, while the levels of LDH, AST and CK- (P <0.05 or P <0.01). Tau treatment group (1000 and 500 mg · kg-1.d-1) increased the activity of SOD (P <0.05 or P <0.01) Disorganization, rupture, dissolution, myofilament lysis, damaged myofascial membrane and disorganized cardiomyocytes resulted in the improvement of myocardial tissue injury in Tau treatment group. ② The levels of LDH, AST, CK and MDA in the myocarditis Tau (400, 200mg · kg-1.d-1) group were significantly decreased and the SOD activity was increased. The levels of Tau (400,200,100mg · kg- -1) decreased the levels of TGF-β1 and TNF-α (P <0.05 or P <0.01). HE staining showed that the myocardial fibrosis was hyperplasia and disorder in ADR model group, Swelling, intracellular edema, mitochondrial structural damage, Tau significantly reduce myocardial damage caused by ADR. Conclusion Tau can protect myocarditis caused by coxsackievirus B3 and ADR through anti-lipid peroxidation and inhibit the expression of TGF-β1 and TNF-α and reduce the occurrence of myocardial fibrosis secondary to ADR myocarditis.