白介素-10基因治疗重症急性胰腺炎的实验研究

目的:探讨重组腺病毒质粒介导的人白细胞介素10(IL10)基因对大鼠重症急性胰腺炎的治疗效果。方法:构建IL10的腺病毒质粒,将其注入健康大鼠腹腔内,检测胰、肝、肺组织内IL10的表达和血清淀粉酶的变化。用5%的牛磺胆酸钠诱发大鼠的重症急性胰腺炎;将IL10腺病毒注入胰腺炎大鼠腹腔内,检测大鼠血清淀粉酶及胰、肝、肺组织内IL10的变化;组织切片观察胰腺组织的病理变化。对照组用空载体和PBS溶液注入腹腔。结果:IL10在健康大鼠组织内有高浓度的表达,转染大鼠并不引起炎症反应。用IL10腺病毒基因治疗24h后,胰腺炎大鼠血清淀粉酶明显降低于对照组;胰、肝、肺组织内的IL10浓度明显高于对照组;TNFα的表达明显低于另两组;病理切片显示治疗组胰腺的炎症改变轻微,而对照组却呈现出血坏死性变化。结论:重组腺病毒介导的人IL10基因治疗可以显著地抑制重症急性胰腺炎的病变,降低死亡率。

Adenovirus-delivered human IL-10 gene in the treatment of severe acute pancreatitis

Objective To evaluate the effect of adenovirus,delivered human interleukin 10 (IL,10) gene in the treatment of severe acute pancreatitis (SAP) in the rat. Methods Healthy SD rats were injected intraperitoneally with adenoviral vector containing IL,10 gene, Adv0 or PBS solution respectively. The level of IL,10 in the pancreas, the liver and the lung were determined by ELISA; serum amylase was assayed at the same time. SAP was induced by injecting sodium taurocholate into the pancreatic duct. The SAP rats received likewise the adenoviral vector containing IL,10, Adv0 or PBS solution. Drugs were administered by a single intraperitoneal injection twenty minutes after SAP had been induced. The level of IL,10 and serum amylase were determined; tissue tumor necrosis factor (TNF,CR; the extent of necrosis and hemorrhage were observed in HE slides. Results The level of IL,10 in the pancreas, liver and lung of healthy rats increased significantly. There was no significant difference in IL,10 level between the two control groups. The contains of IL,10 in the pancreas, the liver and the lung were increased significantly in the IL,10 treatment group, in contrast to the two SAP groups. The serum amylase level was normal in the IL,10 transfected healthy rat group and was down regulated in the IL,10 treated SAP rats comparing with the two SAP control groups. The TNF,pancreas in the IL,10 treated group were remarkably attenuated as compared to the two control groups. Conclusion Adenovirus,delivered human IL,10 gene can decrease significantly the severity of SAP and reduce its mortality.