DMN所致小鼠肝损伤模型中血清IL_18和肝脏Fas mRNA的表达

Expression of Serum IL-18 and Fas mRNA of Liver in Mice Hepatic Injury Model Induced by Dimethylnitrosamine

目的 :观察二甲基亚硝胺 (DMN)诱导实验性肝损伤模型过程中 ,小鼠血清IL_18及肝脏FasmRNA表达的动态变化及其意义。方法 :以0 1 %DMN腹腔注射制备小鼠实验性肝损伤模型 ,以原位末端标记技术(TUNEL)检测肝组织细胞的凋亡 ,ELASA法测定血清IL -18水平 ,半定量逆转录聚合酶链反应 (RT -PCR)检测肝组织FasmRNA的表达。结果 :第1次注射后2d ,即可见散在肝组织细胞凋亡 ,并不伴随明显的炎症和坏死。随着注射次数的增加 ,凋亡及炎症损伤并存且逐渐加重 ,血清IL -18及肝脏FasmRNA的表达水平皆随着肝损伤的加重而增强 ,均于第5次注射DMN后达到最高峰(P<0.01) ,恢复期内明显回落 ,且2者呈正相关趋势 (r=0.407,P<0.05)。结论 :DMN即可诱导肝脏细胞凋亡 ,又可诱导坏死 ,但凋亡在肝损伤的早期机制中更加重要。IL -18的促炎症效应和Fas系统的促凋亡效应之间存在正反馈途径。

Objective:To observe the expression of serum IL-18 and mRNA and its significance in dimethylnitrosamine(DMN)induced hepatic injury.Methods:Liver injury model of mice was created by intraperitoneal injection of 0.1%DMN.Apoptosis of liver was detected by TUNEL,serum IL_18 level was determined by ELASA,and Fas mRNA was observed by RT_PCR. Results:Quite a few apoptotic cells were found in liver after the first injection without obvious inflammation and necrosis,and the degree of apoptosis and inflammatory injury increased notably with more injections.The expression of IL_18 and Fas mRNA correlated with the severity of liver injury,and a positive relationship existed between them(r=0.407,P<0.05). Conclusion:DMN can induce both necrosis and apoptosis in liver tissue,but the latter may play an important role at the early stage.A positive feedback loop existed between the effects of Fas system and IL_18,which aggravated and accelerated this type of liver injury.