Zhiyixiao Express On PI3K-Akt-mTOR Signaling Pathway Of NAFLD And The Study Of Serum Metabolomics

Objective The Experiments using clinical medicine prescription ZhiYiXiao to intervent rat model of NAFLD,based on Traditional Chinese medicine theory,Use of modern scientific techniques of biochemical,pathological,metabolomics,etc to Observe after Z hiYiXiao treatment of rats fed by high-fat die.Observing laboratory parameters,It focus on PI3KmRNA,mTORmRNA gene expression changes in PI3K-Akt-mTOR signali ng pathway and Changes in serum metabolic pathways.At the same time,studing m etabolomics and looking for different metabolites in rat with NAFLD.To investigate t he pathogenesis of NAFLD and medical treatment of NAFLD mechanism.Methods NAFLD models were established using rats fed high-fat diet,60 male SD rats were randomly divided into six groups,which were respectively represent the low dose of treatment groups of ZhiYiXiao,medium dose of treatment groups of ZhiYiXiao and high dose of treatment groups of ZhiYiXiao.YiShanFu capsule positive control group and sodium chloride negative control group,normal control group.normal control group was given a standard diet,others were given high fat diet.During the experimental,feeding interventions were given different conditions,the Rats in group low dose of treatment groups of ZhiYiXiao,medium dose of treatment groups of ZhiYiXiao and high dose of treatment groups of ZhiYiXiao were respectively fed with low,medium and high dose of "ZhiYiXiao",which correspondingly are 3,6 and 12 times of the clinical use for the adult people.in the group YiShanFu were fed with YiShanFu solution,which is 6 times of the dose for the adult peopleThe Rats in the group negative control group and normal control group were fed with normal saline each day.Modeling with high fat and intervention rats were killed after 12 weeks,weighing liver wet weight;collection of blood and liver tissue,Series indexes were detected,For the detection of serum marker of hepatic function and liver homogenates of triglyceride and cholesterol levels.In the light microscope,found pathological changing liver tissue.The qRT-PCR assay was employed to detect the expressions of PI3K/mTOR mRNA,NAFLD serum metabolomics analysis method based on mass spectrometry and-in liquid chromatography,Combined with multivariate data analysis methods,Preliminary finding differences NAFLD serum metabolites.Results Serum biochemical test results show,Compared with the normal group,ZhiYi Xiao in medium dose groups,high dose groups and YiShanFu group there was no sig nificant difference(P>0.05).There are significant differences with the low dose of tre atment groups and the modle group(P<0.01,P<0.05).medium dose groups compare wit h YiShanFu,serum chol decreased significantly(p<0.05).Liver homogenates of TC,TG t est results showed that,compared with the model group,ZhiYiXiao of each dose grou p and YiShanFu was significantly lower(P<0.05).Liver pathology showed,The model a nd ZhiYiXiao of each dose group and YiShanFu group showed varying degrees of lesi on.ZhiYiXiao in all dose groups in liver tissue PI3K,mTOR mRNA expression was significantly lower than the model group(P<0.01,P<0.05),Experimental results show that serum meta bolomics,model group and the normal group differences in the metabolic network,mai nly in fatty acid metabolism,amino acid metabolism and lipid metabolism.After ZhiYi Xiao treatment,metabolic profiling wascloser to the normal groupConclusion Appropriate concentration of traditional Chinese medicine prescription ZhiY iXiao can significantly improve liver function and regulate lipid metabolism.To improv e the deposition of lipids in rat liver NAFLD.Zhiyixiao therapy can control and reduc e liver steatosis and lobular inflammation and periportal inflammatory cell infiltration ZhiYiXiao may regulate the expression of PI3KmRNA,mTORmRNA to make a differe nt of PI3K-AKT-mTOR pathway;the metabolomics shows,differences in NAFLD rat ser um metabolic networks between model and normal,Differentation are mainly fatty acid metabolism,lipid metabolism,amino acid metabolism.After Zhiyixiao treatment,compar ed to the model group,the themetabolic profiling was closer to normal,suggest that dru gs effective regulation of metabolic pathway.