Correlations between inflammatory response, oxidative stress, intestinal pathological damage and intestinal flora variation in rats with type 2 diabetes mellitus

OBJECTIVE To explore the correlations between inflammatory response, oxidative stress, intestinal pathological damage, and intestinal flora variation in rats with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS A total of 80 specific pathogen-free (SPF) male Sprague-Dawley (SD) rats purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijiing, China) were randomly divided into two groups, namely T2DM group (n=40) and normal group (n=40). Then, the contents of inflammatory factors [high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α)] and oxidative stress indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] were detected. Meanwhile, the distributions of intestinal florae Bifidobacteria, Escherichia coli, Lactobacilli and Enterococcocci and the variation of endotoxin were compared between the two groups. Besides, colon specimens were pathologically examined to observe the occurrence of chronic inflammation variation, intestinal mucosal erosion, intestinal mucosal wall thickening and intestinal mucosal fibrosis. Next, the influences of the glycosylated hemoglobin on levels of hs-CRP, MDA and endotoxin and colonization ability of intestinal florae were analyzed. Additionally, univariate and multivariate analyses were performed for underlying the relations of the pathogenesis of T2DM in rats with their inflammatory response, antioxidant capacity, endotoxin level and intestinal flora colonization capacity. RESULTS The levels of hs-CRP and TNF-α were significantly higher in T2DM group than those in normal group (p<0.05). T2DM group exhibited an overtly elevated MDA level (p<0.05), and a clearly lowered SOD level (p<0.05) in comparison with normal group. As to intestinal flora-related indicators, the levels of endotoxin, Escherichia coli and Enterococcocci were evidently higher in T2DM group than those in the normal group (p<0.05), while the levels of Bifidobacteria and Lactobacilli in T2DM group were remarkably lowered (p<0.05). Pathological lesions, including chronic inflammation variation, mucosal erosion, mucosal wall thickening and mucosal fibrosis in intestinal mucosal tissues, were worse in T2DM group than those in the normal group (p<0.05). In T2DM rats, the level of glycosylated hemoglobin was positively correlated with changes in the levels of hs-CRP, MDA and endotoxin (p<0.05), and negatively associated with changes in colonization ability of intestinal florae (p<0.05). Aggravated inflammatory response, decreased antioxidant capacity, increased endotoxin level and weakened colonization ability of intestinal florae were independent risk factors for T2DM in rats. CONCLUSIONS Rats with T2DM have significantly aggravated inflammatory response, weakened antioxidant capacity, imbalanced intestinal florae and markedly pathological changes of intestinal mucosa.