白细胞介素-18在实验性重症急性胰腺炎肝损伤中的作用

Role of Interleukin-18 in Experimental Severe Acute Pancreatitis Complicated with Liver Injury

背景:白细胞介素(IL)-18是一种新发现的促炎细胞因子,其血清水平与重症急性胰腺炎(SAP)合并肝损伤明显相关,然而关于其在SAP急性损伤肝组织中的变化和意义鲜有报道。目的:研究IL-18在SAP大鼠肝组织中的表达,探讨IL-18在SAP肝损伤中的作用。方法:以4%牛磺胆酸钠胰胆管逆行注射诱导大鼠SAP模型。32只大鼠随机分为对照组和SAP6h、12h、18h组。动态测定血清淀粉酶、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平和腹水量;光学显微镜下观察胰腺和肝组织损伤情况;以免疫组化方法检测IL-18在肝组织中的表达和定位;以蛋白质印迹法检测肝组织中IL-18前体和成熟IL-18的表达。结果:SAP组各时间点血清淀粉酶、ALT、AST水平均明显升高,腹水量增多,与对照组相比差异有统计学意义(P<0.01),与胰腺和肝脏的组织病理学改变相一致。造模后IL-18在肝脏Kupffer细胞胞质中呈强阳性表达,阳性Kupffer细胞数增多,成熟IL-18表达明显增加,各时间点与对照组相比差异均有统计学意义,以12h组为著(P<0.01)。结论:Kupffer细胞是肝脏成熟IL-18的主要来源,成熟IL-18表达上调可能在SAP早期肝损伤中发挥重要作用。

Intedeukin （IL）-18 is a newly discovered proinflammatory cytokine, whose serum level is closely associated with liver injury during severe acute pancreatitis （SAP）, however, few studies have focused on its changes and significance in the impaired liver tissue. Aims： To investigate the expression of IL-18 in liver tissue of SAP rats and to appraise the role of IL-18 in liver injury during SAP. Methods： A rat model of SAP was induced by retrograde infusion of 4% sodium taurocholate into the biliary-pancreatic duct. Thirty-two rats were randomly divided into four groups： control group, SAP 6 h, SAP 12 h and SAP 18 h groups. The levels of serum amylase, alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and amount of ascites were determined dynamically. The pancreatic and liver injuries were observed by light microscopy. The expression and distribution of precursor and mature IL-18 in liver tissue were measured by immunohistochemistry and Western blotting. Results： The levels of serum amylase, ALT, AST and amount of ascites increased significantly in the 6 h, 12 h and 18 h SAP groups, statistically higher than those in the controls （P〈0.01）. These changes were paralleled with the histopathological changes of pancreatic and liver tissues. The intensive expression of IL- 18 was located in the cytoplasm of Kupffer cells in liver tissue, and the number of positively stained Kupffer cells and expression of mature IL-18 increased significantly in the 6 h, 12 h and 18 h SAP groups when compared with those in the controls, especially in the 12 h group （P〈0.01）. Conclusions： Kupffer cells are the main source of mature IL-18 in liver tissue. Overexpression of mature IL-18 may play a pivotal role in the pathogenesis of SAP complicated with liver injury.