激活素A及其ⅡA型受体在ConA诱导小鼠急性肝损伤时的表达及其作用

Expression and Role of Activin A and Its Type ⅡA Receptor in Concanavalin A-induced Hepatic Injury in Mice

目的探讨激活素A(ActivinA)及其ⅡA型受体(ActRⅡA)在刀豆蛋白A(ConA)诱导小鼠急性肝损伤时的表达及其作用。方法尾静脉注射ConA诱导小鼠急性肝损伤,测定血清转氨酶水平判断肝脏组织损伤程度,实时定量RT-PCR检测ActivinA及ActRⅡAmRNA转录水平;应用抗ActivinA和ActRⅡA抗体进行阻断试验,测定血清转氨酶水平,HE染色观察肝组织病理学变化。结果ConA诱导的急性肝损伤模型小鼠血清转氨酶水平明显升高,ActivinA及ActRⅡAmRNA转录水平也明显高于对照组;体内应用抗ActivinA和ActRⅡA抗体阻断ActivinA和ActRⅡA的作用,均可不同程度减轻肝损伤。结论ActivinA是介导ConA诱导小鼠急性肝损伤的重要致病因子,阻断ActivinA的表达或其作用途径,可能成为治疗肝损伤疾病的有效靶点。

Objective To investigate the expression and role of Activin A and its type ⅡA receptor（ActRⅡA）in concanavalin A （ConA）-induced hepatic injury in mice. Methods Liver injury was induced in mice by i.v. injection with ConA. The serum ALT and AST levels were determined to assess the severity of liver damage. The transcription levels of Activin A and ActRⅡA mRNAs were determined by real-time quantitative RT-PCR. Blocking tests were performed by using antibodies against Activin A and ActRⅡA, the serum ALT and AST levels were determined, and the pathological change of liver tissue was observed by HE staining. Results The serum ALT and AST levels of mice with ConA induced hepatic injury increased remarkably. Both the transcription levels of Activin A and ActRⅡA mRNAs of model mice were significantly higher than those of control. The blockade of action of Activin A and ActRⅡA by specific antibodies against ActivinA and ActRⅡA attenuated the severity of liver damage at different degrees. Conclusion Activin A is an important pathogen mediating the ConAinduced hepatic injury in mice. The blockade of expression or action mechanism of Activin A may be an effective target to treatment of liver diseases.