Objective To explore the effect of hypoxic training on the barrier function of intestinal mucous membrane and underlying mechanism in rats.Methods Eighty 5-week-old male Sprague-Dawley rats were randomly divided into a control group,an exercise training group,a hypoxia control group and a hypoxia exercise group,each of 20.The altitude training was conducted through swimming training in artificial hypoxia environment.Two and 6 weeks after the intervention,the tissue structure and ultrastructure of small intestine mucosa were observed.The content of diamine oxidase (DAO)and D-lactate (D-LA),tumor necrosis factor-α (TNF-α)and nuclear factor κB (NF-κB)in plasma and the mRNA level of occludin in ileal tissue were measured.Results (1)Electron microscopy data showed that,after six weeks,compared with the control group,the microvilli of rats in the exercise training group were sparser and arranged irregularly.Furthermore,the gap between epithelial cells became wider.In addition,the number of mitochondria decreased significantly and cristae were vague.For the hypoxia control group,the microvilli shortened significantly and arranged irregularly.Moreover,the gap between cells became wider with partial denatured mitochondria.For the Hypoxia exercise group,the number of mucosal epithelium microvilli in the bowels reduced significantly and the microvilli shortened significantly.Similar to that of the hypoxia control group,the gap between epithelium cells growed wider.However,the cellular structure were fuzzier,and the denature of mitochondria worsened,with the cristae being vague even disappearing partially.(2)Two weeks of exercise training reduced the number of intestinal microvilli significantly (P＜0.01),but increased the plasma level of the DAO and D-LA,as well as the expression level of NF-κB in intestinal tissue significantly (P＜0.05).Hypoxic exposure significantly reduced the mRNA level of oceludin in small intestine (P＜0.01),but significantly increased the plasma level of DAO and D-LA (P＜0.05 vs.control)and the expression of TNF-α and NF-κB in small intestine (P＜0.01).There was no significant interaction between two weeks of exercise training and hypoxia exposure either on the reduction of the number and height of intestinal microvilli,or the transcription level of occluding in small intestine,or the plasma level of DAO and D-LA,or the expression of TNF-α and NF-κB in small intestine (P＞0.05).(3)Both exercise training for six weeks and hypoxia exposure significantly reduced the number and height of microvilli in small intestine (P＜0.01)and the occludin level in small intestine,but significantly increased the plasma level of DAO and DLA (P＜0.01),the expression of TNF-α (P＜0.01,P＜0.05)and NF-κB (P＜0.01).Meanwhile there was significant interaction between six-week exercise training and hypoxia exposure on decreasing the number (P＜0.01)and the height (P＜0.05)of microvilli in small intestine.Conclusion (1)Both intensive training and hypoxia exposure can impair intestinal mucosal barrier function and the extent of damage is correlated with the duration of training and hypoxia exposure.(2)Hypoxic exposure and intensive training may reduce the expression of occludin mRNA through increasing the expression of TNF-α and NF-κB in the small intestine,which in turn increases intestinal permeability and intestinal mucosa inju