Caspase-1抑制剂对实验性重症急性胰腺炎肝损伤的保护作用

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (7): 758-763.

Caspase-1抑制剂对实验性重症急性胰腺炎肝损伤的保护作用

张晓华, 朱人敏, 季洪赞, 杨妙芳, 孙泉, 吴晓蔚, 许小兵

南京军区南京总医院消化内科, 南京 210002, 江苏

收稿日期:2008-01-15 修回日期:2008-04-25 出版日期:2008-07-26 发布日期:2020-10-14
作者简介:张晓华,男,医学博士,教授,主任医师,硕士生导师,研究方向:急性胰腺炎发病机制与防治。Tel:025-80860027 E-mail:jszhxh@sina.com
基金资助:
南京军区南京总医院科研课题基金资助项目(2005030)

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

ZHANG Xiao-hua, ZHU Ren-min, JI Hong-zan, YANG Miao-fang, SUN Quan, WU Xiao-wei, XU Xiao-bin

Department of Gastroenterology, Nanjing General Hospital of Nanjing Command, Nanjing 210002, Jiangsu, China

Received:2008-01-15 Revised:2008-04-25 Online:2008-07-26 Published:2020-10-14

摘要/Abstract

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-18mRNA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-18mRNA的表达显著下调(P<0.01vsSAPS),Caspase-1mRNA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。

关键词: 重症急性胰腺炎, 肝损伤, Caspase-1, 白介素-1β, 白介素-18

Abstract: 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-18may play pivotal roles in the pathogenesis of liver injury and Caspase-1 inhibitor improves liver functions effectively in experimental SAP.

Key words: severe acute pancreatitis, liver injury, Caspase-1, Interleukin-1β, Interleukin-18

中图分类号:

R965.2

张晓华, 朱人敏, 季洪赞, 杨妙芳, 孙泉, 吴晓蔚, 许小兵. Caspase-1抑制剂对实验性重症急性胰腺炎肝损伤的保护作用[J]. 中国临床药理学与治疗学, 2008, 13(7): 758-763.

ZHANG Xiao-hua, ZHU Ren-min, JI Hong-zan, YANG Miao-fang, SUN Quan, WU Xiao-wei, XU Xiao-bin. Protective effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(7): 758-763.

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