Caspase-1抑制剂对重症急性胰腺炎大鼠肝IL-18表达的影响  

Effects of Caspase-1 inhibitor on the expression of hepatic interleukin-18 of rats with experimental severe acute pancreatitis

作　　者：朱人敏[1] 史薇[1] 张晓华[1] 袁柏思[1] 杨妙芳[1] 王琳[1] 

机构地区：[1]南京军区南京总医院消化内科,南京210002

出　　处：《解放军医学杂志》2008年第10期1176-1179,共4页Medical Journal of Chinese People's Liberation Army

基　　金：南京军区南京总医院科研基金资助项目(2005030)

摘　　要：目的观察Caspase-1抑制剂对重症急性胰腺炎(SAP)大鼠肝组织及肝内IL-18表达的影响。方法采用4%牛磺胆酸钠逆行注入胰胆管诱发SAP模型。SD大鼠42只,随机分为3组:对照组(HC组,n=6);SAP造模+生理盐水组(SAP-S组,n=18);SAP造模+Caspase-1抑制剂组(SAP-ICE-I组,n=18)。SAP-S组于造模后2h腹腔注射生理盐水1ml,12h后重复1次;SAP-ICE-I组于造模后2h腹腔注射ICE抑制剂,12h后重复1次。HC组模拟胰胆管穿刺操作,但不注射药物。SAP-S组与SAP-ICE-I组于造模后6、12、18h心脏穿刺抽血,测血清淀粉酶(AMY)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,并测定腹水量,留取标本在光镜下观察胰腺及肝组织病理学改变,采用免疫组化方法检测IL-18在肝脏中的表达和定位,并用Western blotting方法检测肝内成熟IL-18蛋白的表达。结果与HC组比较,SAP-S组与SAP-ICE-I组血清AMY、ALT、AST水平明显升高,腹水量明显增多(P<0.01);与SAP-S组相比,SAP-ICE-I各组血清AMY、血清ALT、AST水平和腹水量有显著下降(P<0.01)。光镜下,SAP-S组胰腺和肝组织病理损害程度随时间明显加重,与SAP-S组相比,SAP-ICE-I组对应时间点胰腺病变程度有所减轻,而肝组织损伤未见明显变化。免疫组化结果显示,Kupffer细胞胞质中IL-18的表达在SAP-S组和SAP-ICE-I组较HC组明显增多,而SAP-ICE-I组较SAP-S组明显减少。Western blotting结果显示,成熟的IL-18表达在SAP-S组各时间点明显升高,与HC组相比均具有显著性差异(P<0.01),SAP-ICE-I组各时间点较SAP-S组显著减少(P<0.01),除6h组外均较HC组无显著差异(P>0.05)。结论Caspase-1抑制剂可以抑制成熟的IL-18蛋白的表达,可以有效改善SAP时受损的肝脏功能。Objective To evaluate the effect of Caspase-1 inhibitor on hepatic tissue and on the expression of hepatic interleukirrl8 of rats with experimental severe acute pancreatitis （SAP）. Methods Forty-two SD rats were randomly assigned into 3 groups., healthy control group （HC, n=6）, SAP＋normal saline group （SAP-S, n=18） and SAP＋ICE inhibitor group （SAP-ICE-I, n=18）. SAP was induced by retrograde infusion of 4% sodium taurocholate into the pancreaticobliliary duct in SD rats. Animals in HC group received similar surgical procedure and duet eannulation hut without sodium taurocholate inoculation. In SAP-S group, rats received the first intrapefitoneal injection of isotonic saline 2 hours after induction of acute pancreatitis, and the same injection was repeated at 12th hour. ICE inhibitor was injected into the rats in SAP-ICE-I group 2 hours after induction of acute pancreafitis, and the same injection was repeated at 12th hour. Blood samples were obtained from the rats in SAP-S and SAP-ICE-I groups via cardiac puncture at 6, 12 and 18h after modeling, respec- tively. The levels of serum amylase （AMY）, alanine aminotransferase （ALT） and aspartate arninotransferase （AST）, and the peritoneal fluid, were detected at these three time points. The histopathology of pancrease and liver were observed under light microscope. Intrahe- patic expression and localization of IL-18 protein were detected respectively by Western blotting and immunohistochemistry. Results Ser- um AMY, ALT, AST and peritoneal fluid were significantly increased in SAP-S and SAP-ICE-I groups compared with those in HC group （P〈0. 01）, but decreased significantly in SAP-ICE-I group compared with those in SAP-S group （P〈0. 01）. The pathologic changes in panerease and liver were exacerbated. The pancreatic injury was less prominent at each time point in SAP-ICE-I group compared with that in SAP-S group, while no change in liver was found. Compared with HC group, the expression of IL-18 protein in Kupffer cell cytoplas

关 键 词：重症急性胰腺炎 半胱氨酸蛋白酶-1 白细胞介素-18 

分 类 号：R576.1[医药卫生—消化系统]