Exploring the mechanism of Inflammation Regulation Formula to protect rats with acute gastrointestinal injury in sepsis based on HMGB1/RAGE signaling pathway
Objective To investigate the mechanism of action of inflammation-modulating formula based on the high mobility group protein Bl(HMGB1)/receptor for advanced glycosylation end-products(RAGE)signalling pathway to protect septic a-cute gastrointestinal injury(AGI)rats.Methods A total of 90 SD rats were selected and randomly divided into sham-operation group,model group,high dose(29.6g/kg)group,medium dose(14.8g/kg)group and low dose(7.4g/kg)group of Inflam-mation Regulation Formula,with 16 rats in each group.The AGI model of sepsis was established,except in the sham-operated group,and the survival rate of rats was observed after drug administration;the intestinal myoelectric activity and the contents of Escherichia coli,Bifidobacterium bifidum,and Lactobacillus lactis in the intestinal tract of rats were determined;the pathological changes of the intestinal mucosal tissues of the rats in each group were measured by Hematoxylin-Eosin Staining(HE)method;the levels of TNF-α and IL-6 were determined using ELISA;the levels of Claudin-1 and ZO-1 proteins were determined by immunohistochemistry;and the mRNA expression of HMGB1 and RAGE was examined using QRT-PCR method.Results Com-pared with the model group,with the increase of the dose of Inflammation Regulation Formula,the survival rate,the slow wave frequency and amplitude of intestinal smooth muscle,the thickness of intestinal mucosa and the height of villi,the content of Bifidobacterium and Lactobacillus in the intestinal tract,and the expression of Claudin-1 and ZO-1 proteins in ileal tissues of the rats in the various groups were significantly elevated(P<0.05).Meanwhile,there was a statistically significant(P<0.05)decrease in the levels of TNF-α and IL-6 in rat serum,the content of E.coli in the intestinal tract,as well as the mRNA ex-pression of HMGB1 and RAGE.Conclusion The ability of Inflammation Tuning Formula to ameliorate intestinal mucosal injury,inhibit inflammatory response and restore homeostasis of intestinal internal environment in septic AGI rats may be related to the fact that Inflammation Tuning Formula regulates the intestinal barrier function through the HMGB1/RAGE signalling axis.
Inflammatory modulation formulaHigh mobility group protein B1/late glycosylation end product receptorA-cute gastrointestinal injury in sepsisIntestinal myoelectric activity