Caspase-1抑制剂对实验性重症急性胰腺炎肺损伤的保护作用

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-18mRNA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.

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

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(SAP-S,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 per...