Research On The Mechanism Of Prediabetes Induced By 3-deoxyglucosone And The Intervention Of Ban-xia-xie-Xin Decoction Based On 'Bacterial-inflammation' Functional Axis

Objective:By observing the relationship between the prediabetes caused by 3DG and the imbalance of intestinal flora and the occurrence of chronic inflammation,the mechanism of prediabetes induced by 3DG is fully demonstrated suggesting that the change of dietary structure leads to the disorder of intestinal flora and eventually lead to metabolic diseases such as diabetes.It not only provide new ideas and targets for the study of the etiology,prevention and treatment of type 2 diabetes,but also provides experimental basis for Ban-xia-xie-xin Decoction in the prevention and treatment of type 2 diabetes and the discovery of its prophase drugs,and provides important experimental basis and clinical reference value for improving the understanding,effective prevention and treatment of diabetes.Methods:after 3DG administration by gavage and Ban-xia-xie-xin Decoction accompanied by 3DG treatment for 2 weeks,blood,feces and tissue samples were collected to determine the levels of insulin,ROS,MDA,SOD,NLRP3,TNF-? and IL-1 ? in plasma,ROS,TNF-? and IL-1 ? levels in islet tissue and colon,E-cadherin and ZO-1 expression in colon were analyzed by immunohistochemistry,and Limulus amebocyte lysate was used to detect the LPS level.The contents of 3DG in colon were detected by HPLC;the microbial information in rat intestine was detected by 16S macrogenomic sequencing.Results:compared with the control group,the levels of ROS,TNF-?,and IL-1 ? in islet tissue increased,the levels of LPS,ROS,TNF-? and IL-1 ?increased in colon,the permeability of intestinal mucosa was increased,and the levels of insulin,ROS,MDA,NLRP3,TNF-? and IL-1 ? in plasma were increased,and SOD levels were decreased.The abundance of Parasutterella,Caprociproducens,Candidatus soleaferrea,Enterrhabdus,Gelria,Aerococcus and Corynebacterium decreased,and the metabolic related functional pathway was inhibited.Compared with 3DG group,the levels of TNF-? and IL-1 ? in colon,LPS,TNF-?,IL-1 ? and NLRP3 in plasma,the abundance of Proteus entericus and Candidatus soleaferrea increased,the metabolism of terpenes and polyketenes was up regulated and the cell motility function was down regulated in Ban-xia-xie-xin Decoction group.Conclusion:3DG treatment of rats shows higher intestinal mucosal damage,which is caused by the change of intestinal microecological structure,oxidative stress damage,increased release of intestinal inflammatory factors into the blood circulation,and reached the level of endotoxemia.The possible mechanism of Ban-xia-xie-xin Decoction on the treatment of IGR is that it improves the intestinal mucosal barrier by increasing the abundance of GLP-2 related bacteria,reduces the level of inflammatory factors in intestinal cavity,and then reduces the systemic inflammatory response and repairs the functions of islet cells.