多黏菌素E诱导肠道菌群失调对肠屏障功能和细菌易位的影响

目的:应用多黏菌素E给小鼠灌胃诱导建立肠道菌群失调动物模型,研究肠道菌群失调对肠黏膜屏障和细菌易位的影响。方法:将20只小鼠随机分为两组,每组10只。实验组采用多黏菌素E按0.2 g/kg加入0.2 ml等渗盐水灌胃,1次/d,连续7 d。对照组用等剂量等渗盐水灌胃,1次/d,连续7 d。实验结束次日观察两组小鼠回肠黏膜病理形态、肠道菌群、回肠黏膜组织紧密连接(TJ)蛋白表达和器官(肝、脾、肾、淋巴结)细菌易位率等。结果:实验组小鼠盲肠黏膜和盲肠内容物的肠杆菌数量显著减少。常规病理检查发现,实验组小鼠回肠黏膜充血明显,绒毛稀疏,尖端有少量上皮坏死脱落,与对照组比损伤明显。透射电镜显示,实验组小鼠回肠上皮TJ的电子致密物质明显减少,TJ破坏。回肠黏膜组织中TJ蛋白Claudin-1、Occludin和ZO-1的表达显著下降,器官细菌易位率显著高于对照组。结论:多黏菌素E灌胃能够诱导肠道菌群失调,且导致肠屏障功能损伤和细菌易位。

Effect of gut flora dysfunction induced by polymyxin E on gut barrier function and bacterial translocation

Objective: The purpose of the present study was to explore the effect of gut flora dysfunction induced by ploymyxin E on gut barrier function and bacterial translocation in mice.Methods: Twenty,adult,male BALB/c mice were randomly assigned into two groups,each of 10.Experimental mice received intragastricly with ploymyxin E(0.2 g/kg in 0.2 ml Normal Saline,q.d)for seven days.The mice in control group were administered into stomach with the same amount of normal saline.Pathomorphological change of intestinal mucosa,gut flora,protein expression of tight junction,the rate of bacterial translocation were observed.Results: Administration with ploymyxin E(experimental group)was associated with a significant decrease(vs Control) in the amount of enterobacteria of cecum mocosa and contents.Experimental mice showed an obvious injury(vs Control) under an optical microscope,such as prominent hyperemia of intestinal mucosa,sparse intestinal villus,and a small amount of necrosis and shedding in villus tip.Under an electron microscope,experimental mice also showed an obvious damage(vs Control) that electron dense material in tight junction of intestinal epithelium decreased.The protein expression of Claudin-1,Occludin and ZO-1 of intestinal mucosa decreased with a significant increase(vs Control)of the rate of bacterial translocation in the experimental group.Conclusion: Polymyxin E by intragastric administration can induce the gut flora dysfunction,furtherly destroy gut barrier function and result in bacterial translocation.