Caspase-1抑制剂对实验性重症急性胰腺炎肝损伤的保护作用  

Protective effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis

作　　者：张晓华[1] 朱人敏[1] 季洪赞[1] 杨妙芳[1] 孙泉[1] 吴晓蔚[1] 许小兵[1] 

机构地区：[1]南京军区南京总医院消化内科

出　　处：《中国临床药理学与治疗学》2008年第7期758-763,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：南京军区南京总医院科研课题基金资助项目(2005030)

摘　　要：目的:评价Caspase-1抑制剂二甲基苯甲酰羟甲酮对实验性重症急性胰腺炎(SAP)肝损伤的保护作用。方法:SD大鼠42只,随机分为3组:健康对照组(HC组,n=6),SAP造模+生理盐水组(SAP-S组,n=18),SAP造模+ICE抑制剂组(SAP-ICE-I组,n=18)。以5%牛磺胆酸钠逆行注入胰胆管诱发SAP模型。SAP-S组于造模后2h腹腔注射生理盐水1mL,12h后重复一次;SAP-ICE-I组于造模后2h腹腔注射ICE抑制剂。HC组模拟胰胆管穿刺操作,但不注射药物。结果:SAP-S组血清ALT、AST及IL-1β水平在6h时分别为(216±58)、(372±38)U/L、(277±45)pg/mL,12h时分别为(397±70)、(548±75)U/L、(309±35)pg/mL,18h时分别为(425±86)、(666±84)U/L、(312±46)pg/mL,显著高于HC组(P<0.01);SAP-ICE-I组3者水平显著降低(P<0.01vsSAP-S)。HC组肝组织可见Caspase-1、IL-1β及IL-18 mRNA表达;SAP-S组3者表达水平显著上调(P<0.01vsHC);SAP-ICE-I组IL-1β及IL-18 mRNA的表达显著下调(P<0.01 vs SAP-S),Caspase-1 mRNA表达则无显著改变(P>0.05)。结论:Caspase-1激活、IL-1β及IL-18的过度表达在SAP肝损伤过程中发挥重要的作用;ICE抑制剂可有效地改善肝脏功能损害。AIM： To assess the protective effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis （SAP）. METHODS： Fortytwo SD rats were randomly divided into 3 groups： healthy controls （HC, n = 6）; SAP-S group （n = 18） ; SAP-ICE-I group （ n = 18）. SAP was induced by retrograde infusion of 5 % sodium taurocholate into the bili-pancreatic duct of SD rats. HC rats underwent same surgical procedures and duct cannulation without sodium taurocholate. In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and repeated after 12 h. In SAP-ICE-I group, rats were firstly given ICE inhibitor intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, this was repeated at 12 h. Surviving rats were killed at certain time points, and all samples were obtained for subsequent analysis. RESULTS： The serum levels of ALT, AST and IL-1β in SAP-S group were （215 ± 58）, （372 ± 38） U/L, （277 ±45） pg/mL at 6 h, （397 ± 70）, （548 ± 75） U/L, （309 ± 35） pg/mL at 12 h, （425 ± 86）, （666 ± 84） U/L, （312 ± 46） pg/mL at 18 h, respectively, which were increased significantly （P 〈 0.01 vs HC）. In SAP-ICE-I group, their levels were decreased significantly （ P 〈 0.01 vs SAP-S）. Intrahepatic expressions of Caspase-1, IL-1β and IL-18 mRNA could be observed in HC, which were increased significantly in SAP-S group （ P 〈 0.01 vs HC）. The expressions of IL-1β and IL-18 mRNA were decreased significantly in SAP-ICE-I group （P 〈 0.01 vs SAP-S）, whereas Caspase-1 mRNA expression had no significant differences （ P 〉 0.05）. CONCLUSION： Caspase-1 activation, and the over production of IL-1β and IL-18 may play pivotal roles in the pathogenesis of liver injury and Caspase-1 inhibitor improves liver functions effectively in experimental SAP.

关 键 词：重症急性胰腺炎 肝损伤 CASPASE-1 白介素-1Β 白介素-18 

分 类 号：R965.2[医药卫生—药理学]