Occludin在重症急性胰腺炎小鼠肠黏膜屏障损伤中表达的实验研究

Experimental investigation on the occludin expression in intestinal mucosal barrier of mice with severe acute pancreatitis

目的:探讨occludin蛋白在重症急性胰腺炎(SAP)小鼠肠黏膜屏障功能损伤中作用的调控机制。方法:采用雨蛙肽和内毒素联合注射法制备小鼠重症急性胰腺炎模型。分为3组:对照组、模型组、二硫代氨基甲酸吡咯烷(PDTC)干预组,18 h后处死动物,比较各组的腹腔内大体改变、肠黏膜病理改变,肠道通透性的变化,肠上皮紧密连接蛋白oc-cludin、NF-κB mRNA表达。结果:重症急性胰腺炎造成了小鼠腹腔内明显炎症反应,肠管水肿,肠黏膜水肿,肠道通透性显著增高,NF-κB特异性阻断剂PDTC能降低肠道损伤,改善肠黏膜水肿,上调肠上皮紧密连接蛋白occludin的表达,降低NF-κB mRNA表达,显著降低肠道通透性,occludin与NF-κB mRNA表达呈显著负相关。结论:紧密连接蛋白oc-cludin在SAP时肠道屏障功能损伤过程中起重要作用。这一作用可能是通过NF-κB的调节作用实现的。

Objective：To investigate the role of occludin in the intestinal mucosal barrier injury in mice with severe acute pancreatitis（SAP）.Methods： Thirty-six BALB/c mice were randomized into groups of normal control,SAP model or intervention.SAP models of mice were prepared by combined administration of caerulein and lipopolysaccharide（LPS）,and the animals in intervention group were intraperitoneally injected pyrrolidine dithiocarbamate（PDTC） at a dose of 100 mg/kg.All experimental animals were killed in 18 h for observing the general condition of peritoneal cavity,change of intestinal villi pathologically and intestinal permeability and detecting the expression of tight junction protein occludin and nuclear factor-κB mRNA（NF-κB mRNA）.Results： SAP resulted in a series of intra-abdominal inflammatory response in the experimental animals with edema of intestine and intestinal mucosa and evidently intensified intestinal permeability.Yet,NF-κB,specific blocking agent of PDTC,was found to have ameliorated intestinal injury and mucosa edema,and could improve the intestinal permeability by up-regulating the expression of occludin but inhibiting NF-κB mRNA,which was inversely correlated between the two factors.Conclusion： PDTC could protect the function of intestinal mucosal barrier from injury caused by SAP,suggesting that NF-κB may play an intermediating role in SAP-induced intestinal failure through upregulating occludin expression.