Effects of rhein on intestinal microbiota imbalance and intestinal barrier damage in rats with acute pancreatitis by regulating the AMPK/mTOR signaling pathway
Objective To observe the effects of rhein on intestinal microbiota imbalance and intestinal barrier damage in rats with acute pancreatitis(AP)by regulating the AMPK/mTOR signaling pathway.Methods Ten rats were randomly collected as the sham operation group,and the remaining rats were injected sodium taurocholate to construct an AP rat model.The AP rats were randomly separated into model group,rhein group(100 mg/kg),metformin group(200 mg/kg)and rhein+metformin group(100 mg/kg Rhein+200 mg/kg Metformin),with 10 rats in each group,administered once a day for 2 consecutive weeks.The rats in model group and sham operation group were given equal amounts of physiological sa-line.ELISA method was applied to detect serum DAO activity,TNF-α and IL-6 levels;H&E staining was applied to detect pathological changes in colon and pancreas tissue;16S rRNA gene sequencing of feces was carried out;Western Blot was applied to detect the expression of colon barrier related proteins and AMPK-mTOR pathway related proteins.Results Compared with the sham operation group,the serum DAO activity,IL-6 and TNF-α levels,pathological injury score of pancreas and colon,AMPK,mTOR proteins,and the abundance of Escherichia coli obviously increased in model group(all P＜0.05),while the Shannon,Simpson,Chao1 indexes,relative abundances of Lactobacillus and Bifidobacteri-um,and levels of ZO-1 and Occludin proteins significantly reduced(all P＜0.05).Compared with the model group,the ser-um DAO activity,IL-6 and TNF-α levels,pathological injury score of pancreas and colon,AMPK,mTOR proteins,and the abundance of Escherichia coli significantly reduced in rhein group(all P＜0.05),while the Shannon,Simpson,Chaol in-dexes,relative abundances of Lactobacillus and Bifidobacterium,and levels of ZO-1 and Occludin proteins obviously in-creased(all P＜0.05).The results of the above indicators in the metformin group were opposite to those in the rhein group;metformin reversed the therapeutic effect of rhein on intestinal microbiota imbalance and intestinal barrier damage in AP rats.Conclusion Rhein may improve intestinal microbiota imbalance and intestinal barrier damage in AP rats by down-regulating the AMPK/mTOR signaling pathway.
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