激活素ⅡA型受体在四氯化碳诱导小鼠急性化学性肝损伤中的表达及其作用  

Expression and critical role of type ⅡA receptor of activin A in carbon tetrachloride-induced acute chemical hepatic injury in mice

作　　者：王东辉[1] 方琳[1] 李晓丽[2] 柳忠辉[3] 

机构地区：[1]长春医学高等专科学校基础医学部,吉林长春130031 [2]吉林大学中日联谊医院药学部 [3]吉林大学基础医学院免疫学系,吉林长春130021

出　　处：《环境与健康杂志》2017年第8期678-681,F0003,共5页Journal of Environment and Health

基　　金：吉林省科技厅项目(20060928-01)

摘　　要：目的探讨激活素ⅡA型受体(ActRⅡA)在四氯化碳化学性诱导小鼠急性肝损伤中的表达。方法将48只清洁级C57BL/6近交系雄性小鼠随机分为2组,分别为对照(橄榄油)组和四氯化碳染毒组,每组24只。采用腹腔注射方式进行一次性染毒,染毒容量为10 ml/kg。检测小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)的活力,采用病理形态学方法观察肝组织损伤程度,采用免疫组织化学染色法及实时荧光定量PCR法分别检测肝组织激活素A(Activin A)和其信号传导分子ActRⅡA蛋白的阳性表达强度及mRNA的表达水平。结果四氯化碳染毒后7 d内小鼠血清ALT、AST的活力和肝损伤面积百分比以及肝脏内Activin A和ActRⅡA蛋白的阳性表达强度和mRNA的表达水平均高于对照组,差异有统计学意义(P<0.05);且四氯化碳一次性染毒后,随着时间的延长,小鼠血清ALT、AST的活力和肝损伤面积百分比以及肝脏内Activin A和ActRⅡA蛋白的阳性表达强度和mRNA的表达水平均呈下降趋势。结论 ActRⅡA作为激活素的主要受体,其表达升高是介导CCl4诱导急性肝损伤的重要致病因素,阻断其作用可能成为治疗急性肝损伤疾病的有效方法。Objective To explore the expression of activin type Ⅱ receptor （ActRIIA） and to clarify its role in carbon tetrachloride （CCl4）-indueed acute liver injury in mice. Methods Forty-eight male C57BL/6 inbred male mlce were randomly assigned to two groups, olive oil solvent control group and CCl4-treated group, 24 mice per group. Mice were administrated with CCl4 olive oil solution at 10 ml/kg body weight via intraperitoneal injection once.The level of serum transaminase was measured by biochemical method and histopathological methods were used to observe the degree of liver injury. The mRNA and protein expression of activin A and its signal transduction molecule AetRIIA were detected by real-time fluorescence quantitative PCR and immunohistochemical staining. Results After CCl4-treatment for seven days, compared with control group, the activities of serum ALT and AST,the injuried liver area percentage,the expression of AetRIIA protein and mRNA in CCl4-treated group were increased significant with statistically significant difference （P〈0.05）. After treatment by CC14 once, as time Prolongation, the activities of serum ALT and AST, the liver area percentage injuried, the expression of AetRIIA protein and mRNA in CCl4- treated group were reduced gradually. Conclusion AS ＇a major receptor of activin, ActR Ⅱ A is an important pathogen mediating the CCl4-induced hepatic injury in mice. The blockade of expression or action mechanism of ActR Ⅱ A may be an effective target to treatment of liver diseases.

关 键 词：肝损伤 四氯化碳 激活素A 激活素ⅡA型受体 

分 类 号：R994.6[医药卫生—毒理学]