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Correlations between inflammatory response, oxidative stress, intestinal pathological damage and intestinal flora
1Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. dr_wangguang@126.com.
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.
Insights
Type 2 diabetes mellitus (T2DM) in rats is linked to increased inflammation, oxidative stress, and gut bacteria imbalance. These factors, along with gut barrier damage, are independent risk factors for T2DM pathogenesis.
Area of Science:
- Biomedical Science
- Gastroenterology
- Endocrinology
Background:
- Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder.
- The interplay between systemic inflammation, oxidative stress, and gut health in T2DM is not fully understood.
- Intestinal dysbiosis and barrier dysfunction are increasingly recognized as contributing factors in T2DM.
Purpose of the Study:
- To investigate the correlations between inflammatory response, oxidative stress, intestinal pathological damage, and intestinal flora variations in a rat model of T2DM.
- To identify key factors contributing to the pathogenesis of T2DM.
Main Methods:
- Utilized a T2DM rat model (n=40) and a normal control group (n=40).
- Measured serum inflammatory markers (hs-CRP, TNF-α) and oxidative stress indicators (MDA, SOD).
- Analyzed intestinal flora composition (Bifidobacteria, E. coli, Lactobacilli, Enterococci), endotoxin levels, and performed colon pathological examinations.
Main Results:
- T2DM rats exhibited elevated hs-CRP, TNF-α, and MDA, with decreased SOD levels compared to controls.
- Significant alterations in gut microbiota were observed, including increased E. coli and Enterococci, and decreased Bifidobacteria and Lactobacilli.
- T2DM rats showed worsened intestinal pathological damage, including inflammation, erosion, thickening, and fibrosis.
- Glycosylated hemoglobin levels correlated positively with hs-CRP, MDA, and endotoxin, and negatively with gut flora colonization.
Conclusions:
- T2DM in rats is characterized by aggravated inflammatory response, weakened antioxidant capacity, imbalanced intestinal flora, and significant intestinal mucosal pathology.
- Inflammatory response, oxidative stress, gut barrier integrity, and intestinal flora composition are critical in T2DM pathogenesis.
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