实验性重症急性胰腺炎Caspase-1激活的细胞因子的表达

Expressions of Caspase-1 activated cytokines in experimental severe acute pancreatitis.

目的 研究实验性重症急性胰腺炎 (SAP) Caspase- 1激活的细胞因子的表达。方法 SD大鼠 32只 ,随机分 4组 :正常对照组 (HC组 )、SAP6 h组、SAP12 h组、SAP18h组。采用 5 %牛磺胆酸钠逆行注入胰胆管诱发大鼠 SAP模型。通过 HITACHI- 715 0型自动生化分析仪检测大鼠血清淀粉酶 ;采用 EL ISA法测定血清 IL- 1β水平 ;酶化学法测定胰腺 MPO活性 ;半定量 RT- PCR检测胰腺 Caspase-1、IL- 1β及 IL- 18m RNA的表达 ;免疫组织化学方法检测胰腺 IL- 1β蛋白的表达。结果 SAP各组血清淀粉酶和 IL- 1β水平显著升高 ,并伴有胰腺组织髓过氧化物酶 (MPO)显著增加 ,与 HC组相比 ,其差异均具有显著性意义 (P<0 .0 1)。HC组胰腺组织内可见 Caspase- 1m RNA表达 ,但 IL- 1β及 IL- 18m RNA的表达较弱 ;SAP各组胰腺组织内 Caspase- 1、IL- 1β及 IL- 18m RNA的表达显著上调 (P<0 .0 1)。 SAP各组 IL- 1β蛋白表达显著增强 ,与 HC组比较差异具有显著意义 (P<0 .0 1) ,而且与 SAP严重程度相一致。结论 Caspase- 1激活的细胞因子 IL- 1β及 IL- 18的过度表达在 SAP发病机制中发挥重要的作用。

Objective To study the expressions of Caspase-1 activated cytokines in experimental severe acute pancreatitis(SAP). Methods Thirty-two SD rats were randomized into four groups: healthy controls(HC),SAP 6 h,SAP 12 h and SAP 18 h. SAP was induced by retrograde infusion of 5% sodium taurocholate into the bili-pancreatic duct in SD rats. HC rats underwent identical surgical procedures and duct cannulation without sodium taurocholate infusion. Serum amylase was measured by an automated HITACHI-7150 analyzer. Serum IL-1β protein was measured by ELISA. Myeloperoxidase(MPO) in the pancreas was measured by enzyme chemistry assay. Intrapancreatic expressions of Caspase-1,IL-1β and IL-18 mRNA were detected by semi-quantitative RT-PCR. IL-1β protein expression in pancreatic tissue was detected by immunohistochemistry. Results The serum amylase and IL-1β protein levels were increased significantly ( P < 0.01 vs HC),with the increase of intrapancreatic MPO after induction of pancreatitis. Intrapancreatic expression of Caspase-1 was observed readily,but IL-1β and IL-18 mRNA expressions were weak in HC. The expressions of Caspase-1,IL-1β,IL-18 mRNA and IL-1β protein were increased significantly in SAP groups ( P < 0.01 vs HC),correlating with the severity of SAP. Conclusions The overexpressions of Caspase-1 activated cytokines IL-1β and IL-18 play a pivotal role in the pathogenesis of SAP.