Analysis Of Clinical Efficacy And Mechanism Of Indomethacin In The Early Treatment Of Acute Pancreatitis

Part ?:Clinical Efficacy of Early Use of Indomethacin on Acute PancreatitisObjective:Several clinical trials have confirmed that indomethacin can effectively prevent post-ERCP acute pancreatitis(AP).This study aimed to investigate the clinical efficacy of early use of indomethacin in AP.Methods:Patients diagnosed with AP who were hospitalized in Peking Union Medical College Hospital from June,2014 to November,2019 were retrospectively enrolled.We compared clinical outcomes between patients who were treated with indomethacin in the early stage(symptom onset to admission<72h,and indomethacin was administered within 24h after admission)and who were not treated with indomethacin during hospitalization.Among non-mild AP patients who were treated with indomethacin clinical outcomes between early use and late use were compared as well.Results:1.A total of 240 patients were enrolled including patients who were treated with indomethacin in the early stage(Indo Group,n=56)and who weren't(Control Group,n=184).Among mild AP patients,early use of indomethacin can better relieve abdominal pain.Among non-mild AP patients,early use of indomethacin can significantly reduce the level of C-creative protein(CRP)during the first week of hospitalization and the length of hospital stay(18.47±9.35 vs 24.63±13.41,P=0.011),as well as BISAP score(1.39±0.79 vs 1.79±0.91,P=0.020)and qSOFA score(0.37±0.49 vs 0.62±0.57,P=0.018)on the 7th day of hospitalization.The percentage of infected(peri)pancreatic necrosis was lowered to some extent(0%vs 9.5%,P=0.113).But it did not reduce the risk of organ failure.Risk of gastrointestinal bleeding(51.4%vs 73.2%,P=0.011)and level of serum creatinine(71.91±23.85 vs 96.58±99.96,P=0.005)were both lower in Indo Group.2.A total of 77 non-MAP patients were included in the comparison between patients who were treated with indomethacin in the early stage(Early use Group,n=38)and those in the late stage(Late use Group,n=39).Early use of indomethacin can significantly reduce the percentage of infected necrosis(0%vs 23.1%,P=0.005)and the length of hospital stay(18.47±9.35 days vs 24.90±15.62 days,P=0.032).Conclusions:AP patients can benefit from the use of indomethacin in the early stage.Early use of indomethacin is relatively safe.Part ?:The Effect of Indomethacin on Intestinal Microbiota in Taurocholate-induced Acute Pancreatitis Mice ModelObjective:To investigate the effect of indomethacin on the disease severity and intestinal microbiota in 5%taurocholate-induced acute pancreatitis(AP)mice model.Methods:We established 5%taurocholate-induced AP model.Indomethacin(8mg/kg)was injected intraperitoneally immediately and 12h after the surgery.Mice were sacrificed 24h after the surgery.Peripheral blood and faeces in the colon were collected.The pancreas and the lungs were harvested.Damages to the pancreas and the lungs by acute pancreatitis were analyzed histologically through H&E staining.The level of amylase(AMY)and lipase(LIP)in peripheral blood was measured.Faeces were sent for 16S rRNA sequencing to identify intestinal microbiota.Results:Pancreatic and pulmonary injury was not alleviated histologically by intraperitoneal injection of indomethacin in taurocholate-induced AP mice model.The level of pancreatic enzymes(AMY&LIP)was reduced,but did not reach a statistically significant level.Gut microbiota was altered after the use of indomethacin.Compared with AP group,the abundance of harmful bacterium including Escherichia-Shigella and Enterococcus was statistically declined,but the abundance of beneficial bacterium including Bifidobacterium and Lactobacillus was not increased.Predicted functional analysis revealed that bacterial invasion of epithelial cells was improved in Indo group.Conclusions:In taurocholate-induced AP mice model,we did not observe a significant protective effect of indomethacin.Indomethacin can alter the intestinal microbiota in AP mice.Remarkably,indomethacin can reduce the abundance of Escherichia-Shigella and relieve bacterial invasion of epithelial cells,which possibly improves the intestinal barrier.