Caspase-1抑制剂对实验性重症急性胰腺炎肺损伤的保护作用  

Protective effects of Caspase-1 inhibitor on lung injury induced by experimental severe acute pancreatitis

作　　者：张晓华[1] 季洪赞[1] 杨妙芳[1] 孙泉[1] 吴晓蔚[1] 许小兵[1] 朱人敏[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1173-1175,共3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(2006021)

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)肺损伤的保护作用。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制作大鼠SAP模型。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。HC组模拟胰胆管穿刺操作,但不注射药物。采用ELISA法测定血清IL-1β水平;半定量RT-PCR检测肺内Caspase-1、IL-1β及IL-18 mRNA的表达,并观察肺湿干重比率及组织病理变化。结果SAP-S组血清IL-1β水平在6h、12h、18h时分别为276.77±44.92、308.99±34.95、311.60±46.51pg/ml,显著高于HC组(P<0.01);SAP-ICE-I组与SAP-S组比较水平显著降低(P<0.01)。HC组肺内可见Caspase-1、IL-1β及IL-18 mRNA表达;与HC组比较,SAP-S组3个时间点的表达水平显著上调(P<0.01);SAP-ICE-I组与SAP-S组比较,IL-1β及IL-18 mRNA的表达显著下调(P<0.01),Caspase-1 mRNA表达则无显著改变。SAP-S组肺湿干重比率比HC组显著升高(P<0.05,P<0.01);且显著高于SAP-ICE-I组(P<0.05)。Caspase-1抑制剂治疗使肺损伤程度减轻。结论Caspase-1的激活、IL-1β及IL-18的过度表达在SAP肺损伤过程中发挥重要的作用;抑制Caspase-1可有效地保护SAP肺损伤。Objective To evaluate the protective effect of Caspase-1 inhibitor on acute lung injury （ALI） induced by experimental severe acute pancreatitis （SAP）. Methods Forty-two SD rats were randomly assigned into 3 groups： healthy controls group （HC, n=6）, SAP＋normal saline group （SAPS, n=18） and SAP＋ICE inhibitor group （SAP-ICE-I, n=18）. SAP was reproduced by retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct in SD rats. In animals in HC group same surgical procedure and duct cannulation were performed but without introduction of sodium taurocholate. In SAP-S group, rats received the first intraperitoneal injec tion of isotonic saline 2h after induction of acute pancreatitis, and the injection of saline was repeated at the 12th hour after induction. In SAP ICE-I group, rats were given ICE inhibitor intraperitoneally 2h after induction of panereatitis. Surviving rats were sacrificed at desig hated time points, and blood and all organs were obtained for subsequent analysis. Serum IL-1β was measured by ELISA. Intrapulmonary expressions of Caspase-1, IL-1β and IL-18 mRNA were detected by semi quantitative RT PCR. The ratios of wet/dry weight and his topathological changes in lung were also evaluated. Results The serum IL-1β levels in SAPS group were 276. 77±44. 92pg/ml at 6h, 308. 99--34. 95pg/ml at 12h and 311.60±46. 51pg/ml at 18h after induction of SAP, respectively, which were increased significantly com pared with that in HC group （P〈0.01）. In SAP-ICE-I group, the level was lowered significantly compared with that in SAP S group （P 〈0. 01）. Intrapulmonary expressions of Caspasel, IL-1β and IL-18 mRNA could be observed in HC group, and they were increased sig- nificantly in SAPS group compared with that in HC group （P〈0.01）. The expressions of IL-1β and IL-18 mRNA were decreased signifi candy in SAP ICE-1 group compared with that in SAP-S group （P〈0.01）, whereas the Caspase-1 mRNA expression showed no signifi- cant difference （P〉0.

关 键 词：重症急性胰腺炎 呼吸窘迫综合征 成人 半胱氨酸蛋白酶-1 白介素-1Β 白介素-18 

分 类 号：R576.1[医药卫生—消化系统]