Clinical Efficacy Evaluation And Mechanism Of Banxia Xiexin Decoction Regulating PI3K/Akt/HO-1 In Treating Gastrointestinal Dysfunction In Sepsis

Objective:This study relies on the Natural Science Foundation of Shandong Province to observe the clinical efficacy of Banxia Xiexin Decoction in treating gastrointestinal dysfunction in sepsis,and to explore Banxia Xiexin Decoction in rats with sepsis from the PI3K/Akt/HO-1signaling pathway The protective effect and mechanism of intestinal injury.Methods:(1)Clinical research: Collect patients with sepsis gastro intestinal dysfunction in ICU and emergency hospitalization of the Ea stern Hospital of Shandong University of Traditional Chinese Medicine from October 2018 to December 2019,sign informed consent,record general information of patients,randomize The treatment group and the control group were included.Both groups of patients were given basic Western medicine treatment.Patients in the treatment group were given Banxia Xiexin Decoction,one dose a day,divided into morning and evening.Observe the two groups of patients before treatment,72 htre atment,and 7 days treatment Intra-abdominal pressure,bowel sounds,serum diamine oxidase,and D-lactate levels at each time node,and an alysis and comparison of APACHE II score,SOFA score,gastrointestinal dysfunction score,TCM syndrome score,and ICU hospital stay before and after treatment,28-day mortality,evaluate the clinical efficacy of Banxia Xiexin Decoction.(2)Experimental study 1: Using the sep sis rat model to study the protective effect of different doses of Ba nxia Xiexin Decoction on intestinal injury in sepsis rats: 90 healthy male SD rats were randomly divided into sham operation group,CLP group and half Xia Xiexin Decoction(low,medium,high)treatment group,18 in each group.The sham-operated group was only switched on and off the abdomen,and the remaining four groups used the CLP method to prepare experimental ratmodels of sepsis.Banxia Xiexin Decoction wasgiven by 3.05g/kg·d-1,6.1g/kg·d-1,12.2g/kg·d-1after the model of the low,middle and high treatment group,the normal group,The CLP gro up was intragastrically given the same volume of normal saline.After24 hours of treatment,rat serum and small intestine tissues were co llected.Observe the general symptoms and survival rate of septic rats in each group,and detect the level of serum diamine oxidase,D-lac tic acid,endotoxin and inflammatory factors(IL-1?,IL-6 and TNF-?)by ELISA;HE staining Observe the pathological structure of intestinal tissues of sepsis rats in each group;the expression of inflammatory factors(IL-1?,IL-6 and TNF-?)in the small intestine tissues of sepsis ratsin each group was detected by immunohistochemistry.(3)Expe rimental study 2: Through the treatment of signaling pathway inhibitors,the protective effect of Banxia Xiexin Decoction on sepsis intestinal injury and the mechanism of regulating PI3K/Akt/HO-1 were demons trated from both positive and negative aspects: 50 healthy male SD rats were selected and randomly divided They were sham operation group(Sham group),model group(CLP)group,Banxia Xiexin Decoction group(BXXX group),LY294002 group,LY + Banxia Xiexin Decoction group(LY+ BXXX group),10 in each group.The sham operation was only performe don and off the abdomen.The remaining four groups replicated the experimental one sepsis rat model.The LY294002 group and the LY + Banx ia Xiexin Decoction group were intraperitoneally injected with LY294002 before modeling.After modeling,the Banxia Xiexin Decoction group and the LY + Banxia Xiexin Decoction group were gavaged at the dose of 12.2 g/kg,and the normal group,CLP group,and LY group were gava ged with equal volume of normal saline.After 24 hours of treatment,rat serum and small intestine tissues were collected.Observe the gen eral symptoms of septic rats in each group;ELISA detected the levels of serum diamine oxidase,D-lactic acid,endotoxin and inflammatory factors(IL-1?,IL-6 and TNF-?)in septic rats in each group;After HE staining,observe the pathological structure changes of the small intestine tissue of sepsis rats in each group;Western Blot method to detect the inflammatory factors IL-1?,IL-6,TNF-? and PI3K,P-Akt inthe small intestine tissue of sepsis rats in each group And HO-1protein expression;q-PCR method was used to detect the expression l evels of IL-1?,IL-6 and TNF-?,PI3K,P-Akt and HO-1m RNA in the inte stinal tissues of septic rats in each group.Result:(1)Clinical research:(1)Banxia Xiexin Decoction can reduce TCM syndrome score,APACHE II score,SOFA score and gastrointestina l dysfunction score in patients with gastrointestinal dysfunction in sepsis(P<0.01),and can improve The total effective rate of dysfunc tion treatment(P<0.01);(2)Banxia Xiexin Decoction can improve intr a-abdominal pressure and bowel sounds in patients with gastrointestinal dysfunction in sepsis,and reduce serum diamine oxidase and D-lact icacid Level(P<0.01);(3)Banxia Xiexin Tang did not significantly reduce the 28-day mortality and shorten the ICU hospital stay(P>0.05),but Banxia Xiexin Tang showed a certain downward trend after trea tment.(2)Experimental study 1:(1)After cecal ligation,the rats devel oped a series of symptoms such as slow movement,unresponsiveness,weakened refusal to arrest,rough hair,messy,yellowing,and eyeball congestion.Each treatment group of Banxia Xiexin Tang The above sympt oms were improved compared with the CLP group;(2)The survival rate of rats in each treatment group of Banxia Xiexin Tang was significantly higher than that of CLP group,and the survival rate of Banxia Xiexin Decoction high-dose group was the highest,and the survival time of rats was longer and better In the other two groups;(3)Banxia Xiexin Decoction significantly reduced the intestinal tissue damage in rats,the pathological score was lower than CLP group,and Banxia Xiexin Tang high-dose group had the least intestinal tissue damage;(4)Banxia Xiexin Decoction Treatment can significantly reduce serum diamine oxidase,D-lactic acid,and endotoxin levels in sepsis rats,and the high-dose group is superior to the other two groups;(5)Banxia Xiexin Decoction treatment can significantly reduce serum and small intestine in sepsis rats The levels of IL-1?,IL-6 and TNF-? were organized in a dose-dependent manner.Experimental Study 2: Compared with the Sham group,the levels of IL-1?,IL-6 and TNF-? in the serum and intestinal tissues of rats in each group increased after CLP,the expression of PI3K,P-Akt and HO-1 increased,and the serum diamine oxidation The levels of enzymes,D-lactic acid and endotoxin increased,and the intestinal injury was severe;compared with the CLP group,the levels of IL-1?,IL-6 and TNF-? in the serum and intestinal tissue of rats after intervention of Banxia Xiexin Decoction decreased,Increased expression of P-Akt and HO-1,decreased levels of serum diamine oxidase,D-lactic acid and endotoxin,reduced intestinal tissue damage;IL-1?,IL-6 and TNF-?in rat serum and intestinal tissue after LY294002 treatment Increase dlevels,decreased expression of PI3K,P-Akt,HO-1,increased levels of serum diamine oxidase,D-lactic acid and endotoxin,intestinal ti ssue damage was more severe than CLP group;compared with Banxia Xiex in Tang group,LY + Serum and intestinal tissue IL-1?,IL-6 and TNF-? levels of rats in Banxia Xiexin Tang group increased,PI3K,P-Akt,HO-1 expression decreased,serum diamine oxidase,D-lacticacid and Internal Toxin levels increase,and intestinal tissue damage is more severe.This study shows that Banxia Xiexin Decoction inhibits inflam mation of the small intestinal tissue during sepsis and reduces intes tinal tissue damage,which may be related to its regulation of PI3K/Akt/HO-1 signaling pathway.CONCLUSIONS:(1)The treatment of Banxia Xiexin Decoction can signi ficantly improve abdominal distension,abdominal pain,nausea and vomiting,constipation,intestinal bowel disease,fever and other clinical symptoms in patients with gastrointestinal dysfunction in sepsis,and can effectively reduce abdominal pressure and restore bowel noise It reduces the criticality of the patient's condition,and the 28-day fatality rate and ICU hospital stay of the patient show a downwardtre nd.(2)Animal experiment studies have found that Banxia Xiexin Decocti on can inhibit the inflammatory response of sepsis rats,reduce the i ntestinal damage of sepsis rats,and improve the survival rate of rats,and is dose-dependent,and this Aprotective effect may be achieved by regulating the PI3K/Akt/HO-1 signaling pathway.