| Objective investigate the clinical efficacy of Yan Tiao Fang in the treatment of acute pancreatitis induced Acute intestinal injury(Fu Shi Re Jie syndrome)and its effect on autophagy related pathway PI3K/AKT/mTOR;Objective to explore the mechanism of Yan Tiao Fang on autophagy related pathway PI3K/AKT/mTOR signaling pathway in rats with acute pancreatitis intestinal injury.MethodClinical research:70 patients with acute pancreatitis(moderate severe,severe)were randomly divided into two groups(traditional Chinese medicine treatment group and control group),35 patients in each group.The control group was treated with conventional western medicine,while the traditional Chinese medicine treatment group was treated with Yan Tiao Fang on the basis of conventional western medicine.The clinical efficacy was evaluated after 10 days of treatment.The TCM symptom score,intra-abdominal pressure,defecation frequency,bowel sounds frequency,blood amylase,urine amylase and inflammatory factors(TNF-α,IL-6,IL-10),PCT,lactic acid,intestinal mucosal oxidative stress injury(ROS,SOD,MDA),autophagy protein(LC3-II,Beclin1),PI3K/AKT/mTOR path index,AGI rating,BISAP score,MCTSI rating,APACHEⅡscore were observed before and after treatment.Experimental study:48 SD rats were randomly divided into sham group,model group,Shanning group and Yan Tiao Fang group,with 12 rats in each group.The model of acute pancreatitis was established by injection of sodium taurocholate.In Shanning group,octreotide was injected subcutaneously into the back of rats immediately after modeling,once every 8 hours;The rats in Yan Tiao Fang group were given Yan Tiao Fang by gavage before modeling.Samples were taken at 6 and 12 hours after modeling in each group,6 at each time point.The histopathological changes of pancreas and small intestine were observed by HE staining.The apoptosis of small intestine was detected by TUNEL.The expression of autophagy related proteins LC3-II and Beclin1 was detected by Western blot and immunofluorescence;The protein expression of PI3K/AKT/mTOR pathway was detected by Western blot;Detection of inflammatory factors in serum and small intestine by ELISA(TNF-α、IL-6、IL-10),oxidative stress(SOD、MDA、ROS),PCT,lactate acid index.ResultsClinical research:in terms of clinical efficacy,the total effective rate of Yan Tiao Fang group was better than that of the control group(P<0.05);In terms of TCM syndrome score,the total score of TCM syndrome in Yan Tiao Fang group was significantly lower than that in the control group from the third day after treatment(P<0.05);Compared with the control group,the main symptoms and concurrent symptoms of Yan Tiao Fang group were improved(P<0.05);In the aspect of gastrointestinal function,the level of intra-abdominal pressure in Yan Tiao Fang group was significantly lower than that in the control group(P<0.05),and the frequency of defecation and bowel sounds per day in Yan Tiao Fang group was significantly higher than that in the control group(P<0.05);In terms of clinical efficacy score,the AGI score,BISAP score,MCTSI score and APACHE II score of the Yan Tiao Fang group were significantly improved compared with those of the control group(P<0.05).In terms of clinical research indexes,the levels of PI3 K,AKT,mTOR,LC3-II,Beclin1,ROS,MDA,TNF-α,IL-6,PCT,blood amylase,urine amylase,blood lactate,leukocyte and CRP in Yan Tiao Fang group were lower than those in control group(P<0.05),The levels of SOD,IL-10 and blood calcium in the treatment group were higher than those in the control group(P<0.05).Experimental study:in the aspect of pancreatic and intestinal injury,the pathological scores of pancreatic and intestinal mucosal tissue injury in Yan Tiao Fang group were significantly lower than those in Shanning group and model group at each time point(P<0.05);The apoptotic index of Yan Tiao Fang group was lower than that of Shanning group and model group at different time points(P<0.05);After treatment,the levels of TNF-α,IL-6,PCT,MDA and ROS in serum and small intestine of Yan Tiao Fang group were significantly lower than those of Shanning group and model group(P<0.05),while the levels of IL-10 and SOD were significantly higher than those of Shanning group and model group(P<0.05);After treatment,the protein levels of LC3-Ⅱ,Beclin1,p-PI3 k,p-AKT and p-mTOR in small intestine tissue of Yan Tiao Fang group were significantly lower than those of Shanning group and model group(P<0.05).Conlusion1.This clinical trial found that:(1)Yan Tiao Fang can better and faster relieve the clinical symptoms and signs of acute intestinal injury patients caused by acute pancreatitis,mainly in the improvement of clinical total effective rate,TCM syndrome score and clinical efficacy score,which are significantly better than the control group.At the same time,it can significantly reduce intra-abdominal pressure,enhance gastrointestinal motility,and promote the recovery of gastrointestinal function.(2)Yan Tiao Fang can alleviate the degree of serum autophagy in patients with pancreatitis,which may improve the damage of autophagy by inhibiting PI3K/Akt/mTOR signaling pathway,so it has the effect of anti-inflammatory,anti oxidative stress,increasing tissue perfusion and protecting organ function.2.The animal experimental study found that:(1)from the pathological observation,Yan Tiao Fang can improve the ischemia,necrosis and inflammation of pancreas and intestinal mucosa in rats with acute pancreatitis.(2)Yan Tiao Fang can effectively inhibit the apoptosis of pancreatic and intestinal mucosa cells,and effectively regulate the degree and scope of intestinal apoptosis,improve the development and prognosis of pancreatitis.(3)In the treatment of acute pancreatitis induced acute intestinal injury Yan Tiao Fang may inhibit PI3K/Akt/mTOR signaling pathway,improve autophagy damage,control inflammatory response and reduce oxidative stress-induced damage,and ultimately protect the pancreatic and intestinal mucosal barrier. |
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