血管活性肠肽对重症急性胰腺炎肠屏障保护作用的实验研究

目的 探讨血管活性肠肽(VIP)对重症急性胰腺炎(SAP)大鼠肠屏障的保护作用及其机制.方法 54只SD大鼠随机分成3组:假手术组(SO)、SAP组和VIP干预组,采用微泵逆行胰胆管注射4%牛磺胆酸钠制备SAP动物模型,SAP制模后5 min腹腔注射VIP 5×10-9nmol作为VIP干预组.各组在制模后1 h、6 h、12 h检测血浆内毒素水平,逆转录(RT)-PCR法及免疫组化法检测肠黏膜Toll样受体4(TLR4)表达,并对肠黏膜组织行电镜检查.结果 与SO组相比,SAP组血浆内毒素和肠黏膜TLR4表达在制模1 h即开始增高,并随制模时间的延长而进行性增高.两者具有明显的相关性.电镜检查肠黏膜有明显的病理损伤.VIP干预组与SAP组同时点相比,血浆内毒素和肠黏膜TLR4表达降低,病理损伤减轻,制模后6 h尤为明显.SO组肠黏膜未见TLR4表达.结论 VIP能有效保护SAP肠屏障功能,其机制可能与下调肠黏膜TLR4的表达有关.

The protective effect of vasoactive intestinal peptide on gut barrier in severe acute pancrititis in rats

Objective To investigate the protective effects of vasoactive intestinal peptide(VIP) on gut barrier in rats with severe acute pancrititis(SAP)and its mechanisms.Methods Fifty-four SD rats were randomly divided into sham operated(So)group,SAP group and VIP group.The model of SAP was induced by retrograde injection of 4%sodium taurocholate into the bili-pancreatic duct.The rats in VIP group were intraperitoneal injected with VIP of 5×10-9 nmol 5 minutes after model established.The endotoxin in plasma was measured at 1,6 and 1 2 hour.The expression of Toll-like receptor(TLR)4 in gut mucosa was examined using RT-PCR and immunohistochemistry and mucosa tissue were detected using electroscopic examination.Results The concentration of endotoxin in plasma and expression of TLR4 were both increased at 1 hour and reached peak at 1 2 hour in SAP group compared with SO group(no expression of TLR4),but were decreased in VIP group.A correlation was found between endot6xin and expression of TLR4.The electroscopic examination showed that the pathological injury in intestine was severe in SAP group than that in VIP group.Conclusion The protective effect of VIP in gut barrier function may contribute tO down-regulation of TLR4 expression in gut mucosa.