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N-乙酰半胱氨酸对重症急性胰腺炎大鼠肠道屏障功能障碍与二次打击的保护作用

N-acetylcysteine prevents intestine barrier functional disturbance and"second attack"following sodiuln taurocholate-induced severe acute pancreatitis in rats

摘要:

目的 观察N-乙酰半胱氨酸(NAC)对重症急性胰腺炎(SAP)大鼠肠屏障功能障碍与二次打击的防护作用.方法 雄性Wistar大鼠54只随机分为SAP组(n=24)、SAP+NAC组(n=24)和假手术组(n=6).建模后3、6、12、24 h,取腹主动脉血液和小肠、胰腺、肺脏、肝脏组织.光镜下观察小肠组织病理改变,检测各时段血浆肿瘤坏死因子(TNF)-α、白细胞介素-6(IL-6)和二胺氧化酶(DAO)活性,以及胰腺、肺脏、肝脏中髓过氧化物酶(MPO).结果 SAP组各时间点血液TNF-α、IL-6、DAO均较假手术组显著升高(P<0.01),6、12、24 h胰腺、肺脏、肝脏MPO较假手术组显著升高(P<0.05或P<0.01);与SAP组比较,SAP+NAC组各时间点血液TNF-α、IL-6显著下降(P<0.05或P<0.01),6、12、24 h三个时间点DAO活性均显著降低(P<0.05或P<0.01),12、24h胰腺、肺脏、肝脏MPO显著减少(P<0.05或P<0.01).结论 NAC可有效防护SAP大鼠肠屏障功能障碍,并可减轻胰腺、肺脏、肝脏遭受二次打击的严重程度.

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Objective To evaluate the protective effect of N-acetylcysteine(NAC)on the small intestinal mucosal barrier and other organs in severe acute pancreatitis(SAP)rats.Methods Fifty-four Wistar male rats were divided into sham operation group(n=6),SAP group(n=24),and SAP+NAC group(300 mg/kg body wt)(n=24).Sham operation group underwent laparotomy only.SAP model was established by retrograde injection of 5%sodium taurocholate into the bile-pancreatic duct in Wistar rats.The rats in SAP+NAC group were administered with NAC 300 mg/kg body wt intaperitoneally 2 h before SAP model establishment.Rats were killed at 3,6,12 and 24 h after operation.The terminal ileum was collected for examination under light microscopy.The samples of the pancreas,the lung and the liver were collected for measuring the levels of myeloperoxidase(MPO).The blood levels of diamine oxidase(DAO).tumor necrosis factor Mpha(TNF-α)and interleukin-6(IL-6)were also measured.Results The contents of TNF-α,IL-6 and DAO in SAP group were increased significantly at all the 4 time points as compared with those in sham operation group(P<0.01).The levels of MPO in the pancreas.the lung and liver of SAP group were increased significantly at 6,12 and 24 h as compared with those in sham operation group(P<0.05 or P<0.01).As compared with SAP group,the contents of TNF-α and IL-6 were signifieanfly decreased in SAP+NAC group at all the 4 time points(P<0.05 or P<0.01),while the level of DAO significantly decreased in SAP+NAC group except for the 3-h time point(P<0.05 or P<0.01).The contents of MPO in the pancreas,the lung and the liver were significantly decreased in SAP+NAC group at 12 and 24 h after operation(P<0.05 or P<0.01).Conclusion NAC may protect the small intestine mucosal barrier and other organs by reducing the polymorphonuclear leucocyte detaining,which might be relate to the reduction of neutrophil aggregation by decreasing the release of TNF-α and IL-6.

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