关键词: 自噬, 慢性肾衰竭, 肠黏膜屏障

Abstract: Objective To observe the injury of intestinal mucosal barrier and the expression of autophagy protein in colon tissue of rats with chronic renal failure. Methods Thirty SPF healthy male SD rats were randomly divided into sham operation group (10 rats) and model group (20 rats). The model group was given adenine 200 mg/(kg·d) by gavage for 4 weeks after left nephrectomy. The general conditions of rats were observed. Serum, renal tissue and colon tissue samples were collected at 4 and 8 weeks after gavage. The levels of serum creatinine, urea nitrogen, TNF-α, IL-6 and LPS were measured by ELISA. Renal and colon tissue were examined by HE staining and microscopy. The protein expressions of LC3, beclin-1, ZO-1 and claudin-1 were detected by Western blot. Results Compared with the sham operation group, the model group rats gradually showed a slow response to external stimuli, slow action, withered and yellow hair color, dull luster, pale conjunctiva and slow weight gain. The levels of serum creatinine, urea nitrogen and inflammatory factors in the model group were all higher than those in the sham operation group, and increased at 8 weeks compared with 4 weeks (P＜0.05). Renal pathology in the model group showed renal tubular dilatation, lymphatic and monocyte infiltration, glomerulosclerosis and interstitial fibrosis. Histopathology of colon in model group showed atrophy and collapse of intestinal villi, infiltration of inflammatory cells in mucosal layer and aggravation of pathological changes, which was more serious at 8 weeks than at 4 weeks. The expression of LC3Ⅱ/Ⅰ, Beclin-1, ZO-1 and Claudin-1 in the model group decreased as compared to those of sham operation group(P＜0.05), and much decreased at 8 weeks as compared with 4 weeks (P＜0.05). Conclusions Autophagy disorder may be a potential mechanism causing intestinal mucosal barrier injury in rats with chronic renal failure.

Key words: autophagy, chronic renal failure, intestinal mucosal barrier