Abstract: 【Abstract】Aims To investigate the effect of intestinal-derived uremic toxin homocysteine (Hcy) on intestinal permeability, barrier structure and barrier function in adeninEinduced uremic rats. Methods SD rats were divided into five groups: normal control (group NC, n=10), Hcy (group H, n=10), uremia (group U, n=10), uremia+Hcy (group UH, n=10), and uremia+Hcy+ probiotic compound preparation VSL#3 (group UHV, n=10). Experimental uremia was induced by intragastric adenine administration and Hcy was injected subcutaneously. Animal models were assessed by renal function and pathological examinations. The pathological
changes of intestinal tissue were observed by H-E staining and electron microscopy. The levels of Hcy, interleukin (IL-6), tumor necrosis factor α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and intestinal tissue, serum endotoxin, and intestinal permeability were assessed. The tight junction proteins of claudin-1, occludin, and ZO-1 were assessed by western blotting. Results Compared with group NC, serum and intestinal tissue levels of Hcy (serum: F=153.666, P＜0.001; tissue: F=44.456, P＜0.001), IL-6 (serum: F=86.845, P＜0.001; tissue: F=89.946, P＜0.001), TNF- α (serum: F=29.782, P＜0.001; tissue: F=23.629, P＜0.001), and MDA (serum: F=52.367, P<0.001; tissue: F=58.976, P＜0.001), serum endotoxin (F= 37.287, P＜0.001), and intestinal permeability (F=50.539, P＜0.001) were significantly elevated, while serum and tissue SOD activity decreased (serum: F=106.538, P＜0.001; tissue: F=114.599, P＜0.001) in the experimental groups, especially in UH group. The most pathological changes of intestinal structure were also found in group UH. The levels of tight junction proteins decreased in the experimental groups. Supplementation with probiotic compound preparation VSL#3 improved oxidative and inflammatory injuries and the expression levels of tight junction proteins. Conclusion Hcy aggravates the damages of intestinal permeability and epithelial barrier by induction of oxidative and inflammatory injuries in uremic rats. Probiotic administration
ameliorates these damages by reduction of Hcy-induced oxidative and inflammatory injuries.

Key words: Homocysteine, Uremia, Intestinal epithelial barrier, Oxidative and inflammation, Probiotics