Caspase-1抑制剂对重症急性胰腺炎大鼠肺IL-18表达的影响

The effect of Caspase-1 inhibitor on the expression of interleukin 18 of lung in experimental severe acute pancreatitis

目的观察Caspase-1抑制剂对重症急性胰腺炎(SAP)大鼠肺组织及肺内IL-18表达的影响。方法将42只SD大鼠随机分为对照组(n=6)、SAP-S组(n=18)和SAP造模+Caspase-1抑制剂组(SAP-ICE-I组)(n=18)。SAP-S组与SAP-ICE-I组于造模后6、12、18h心脏穿刺抽血,动态监测血清淀粉酶、肺湿干重比率,光镜下观察胰腺及肺组织病理学改变,采用免疫组化和Western blotting方法检测肺内IL-18的表达情况。结果 SAP-ICE-I各组血清淀粉酶、肺湿干重比率较SAP-S组有显著下降(P<0.01)。光镜下,SAP-ICE-I组对应时间点胰腺和肺组织病理损害程度较SAP-S组明显减轻。免疫组化和Western blotting结果显示,SAP-ICE-I组各时间点IL-18较SAP-S组显著减少(P<0.01),但均显著高于对照组(P<0.01)。结论 Caspase-1抑制剂可以抑制成熟的IL-18蛋白表达,有效改善SAP时的肺损伤。

Objective To assess the therapeutic effect of Caspase-1 （called interleukin-113 converting enzyme, ICE ）inhibitor on acute lung injury （ALI） in experimental severe acute pancreatitis（SAP） and the expression of interleukin 18 in the lung. Methods Forty-two SD rats were randomly divided into 3 groups： healthy controls, SAP-S group and SAP-ICE-I group. The rats were sacrificed after operation at 6, 12 and 18 hours. The levels of serum amylase （AMY）, ratio of lung weight wet to dry were measured. The expression of IL-18 in lung tissue was measured by immunohistochemistry and Western blotting. Results There were decrease of serum AMY and ratio of lung weight wet to dry in SAP-ICE-I group at 6 h, 12 h, 18 h significantly compared with those in the SAP-S group （P〈0.01, P〈0.05）. The expressions of IL-18 protein was decreased significantly in SAP-ICE-I group compared with those in the SAP-S group （P〈0.01）. Conclusion Caspase-1 inhibitor can reduce the expression of IL-18, and reduced lung lesion from ALI in experimental SAP.