激活素相互作用蛋白5在急性肝损伤动物模型中的表达变化及意义

ActRIP5 expression and significance in animal model of acute liver injury

目的探讨激活素及激活素相互作用蛋白5(Act RIP5)在刀豆蛋白A(Con A)诱导动物的急性免疫性肝损伤进程中的表达变化及意义。方法 C57BL/6小鼠尾静脉注射Con A(15 mg/kg),分别于给药后不同时段分批次检测模型动物血清酶学改变、肝脏脾脏形态及指数变化、肝脏组织病理学改变,应用实时荧光定量聚合酶链反应(q RT-PCR)检测激活素及Act RIP 5的表达变化。结果 Con A诱导的肝损伤模型血清丙氨酸转氨酶(ALT)、天冬氨酶转氨酶(AST)在给药后4 h开始升高,给药后24 h达到高峰,后逐渐下降,96 h仍未达到正常水平;小鼠脾脏指数自给药后2 h开始增加,24 h达到峰值,48 h开始下降,96 h恢复正常水平;肝脏指数自给药后24 h开始增加,48 h达到最大值后开始下降,96 h仍未恢复正常。形态学及病理学检测显示给药后4 h开始出现肝脏损伤,24~48 h损伤最严重,48 h后损伤开始修复,96 h仍未恢复至正常水平;q RT-PCR结果显示激活素在给药后2 h开始升高,8 h达峰值后开始下降,96 h降至正常水平;Act RIP5给药后4 h开始上升,8 h达到峰值后开始下降,96 h未降至正常水平。结论 Con A可诱导急性肝损伤,激活素及Act RIP 5的表达于肝损伤进展期异常升高,肝损伤恢复期下降并恢复至正常,提示激活素可能通过其肝内特异信号传导Act PIR5参与了Con A诱导的急性肝损伤。

Objective To investigate the expressions and significance of activin and activin receptor-interacting protein 5 （ActRIP5） in the process of animal acute immune liver injury induced by concanavalin A （ConA）. Methods ConA （15 mg/kg） was injected into C57BL/6 mice through tail vein. In different periods after administration of ConA, the changes of serum enzymes, and liver and spleen morphology and indexes were determined in the model mice, the expressions of activin and ActRIP 5 were detected by fuorescence quantitative PCR. Results The serum levels of ALT and AST in the liver injury model began to increase 4 h after ConA injection and reached the peak in 24 h, then gradually decreased, but did not yet return to the normal level in 96 h. The spleen index of the mice began to increase 2 h after administration and reached the peak after 24 h, and began to decline after 48 h, and returned to the normal level after 96 h. The liver index began to increase 24 h after administration and reached the maximum after 48 h, then began to decrease, and did not return to normal yet after 96 h. The morphological and pathological examination revealed that liver injury began to appear 4 h after administration and was most serious between 24 h and 48 h, and began to recover after 48 h, but did not return to normal yet after 96 h. Fluorescence quantitative PCR results showed that activin A began to decline 2 h after administration and reached the peak after 8 h, then began to decrease, and got to the normal level afeter 96 h; ActRIP5 began to rise 4 h after administration and reached the peak after 8 h, then began to decline, but did not return to the normal level after 96 h. Conclusions ConA can induce acute liver injury. The expressions of activin and ActRIP5 abnormally elevate during the progressive stage of liver injury, and decrease and return to normal during the recovery period of liver injury, suggesting that activin may participate in ConA-induced acute liver injury through the specifc signal transduction protein ActPIR5.