Study About The Intestinal Mechanism Involved In The Anti-hyperglycemic Effect Of Rhein

BackgroudRhein, an anthraquinone compound isolated from rhubarb, has been used in traditional Chinese medicine with putative anti-diabetic effects. our research group had found that Rhein could significantly reduce plasma glucose in diabetes mice (db/db), improving the insulin resistance, inhibiting the islet cell oxidative stress damage, protecting islet beta cell function. However, the mechanism remains unknown. Recent studies had shown that gut microbiota played an essential role in the metabolic diseases such as type 2 diabetes and obesity. Gut microbiota refers to all the bacteria that resided in the gut. It affects lots of the biological functions throughout the body and has become a major research area in biomedicine. Gut microbiota also plays an important role in the process of type 2 diabetes, inflammatory bowel disease, obesity, coronary heart disease and so on. A research based on 16S rDNA suggested that Firmicutes and Clostridia significantly reduced in the diabetic subjects. A metagenome-wide association study (MGWAS) shown that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. Antibiotics could affect the glucose by modulating the intestinal microbiota. A study demonstrated that mice treated with antibiotics for five weeks shown the improved glucose tolerance than the controls without significantly affecting the weight. Weight-loss surgery can significantly change the composition of gut microbiota, rats with Roux-en-Y gastric bypass surgery had decreased firmicutes and increased Bifidobacterium accordingly. Current progress suggests that gut microbiota plays a fundamental role in the mechanism of oral anti-diabetic medications. This study has two part to observe the influence of Rhein on intestinal flora in db/db mice and db/m mice as well as on the plasma Glucagon-like peptide 1, GLP-1. Furthermore, to explore the relationship between gut microbiota and Rhein, opening a new way for analysising the mechanism traditional Chinese medicine.ObjectivePart1. To study whether Rhein affect the intestinal microbial composition of type 2 diabetes model (db/db mouse) and normal control model (db/m mouse). Part2. To observe the active GLP-1 in the plasma of db/db mice and analyze its relevance to Desulfovibrio.MethodsPart1. The db/db mice and db/m mice, fed with normal-chow diet, were randomly divided into drug group and model control group respectively and gavaged with Rhein (120mg/Kg) or sodium cellulose (0.1%) everyday. The mice fecal samples were collected aseptically in the 0,2,3 week of the experiment. The composition of the gut microbiota was assessed by analysing 16S rDNA gene sequences and the divisity of the gut microbiota was evaluate by shannon index. Part2. The active GLP-1 was assessed by ELISA and statistical analysis was performed by SPSSStatistic.22.Results:Part1. The becteroids in the groups teated with Rhein increased obviously whereas the firmicutes decreased. The divisity s was lower after the Rhein treatment as well. Part2 The active GLP-1 in the plasma of Rhein treatment mice elevated significantly.