Study On Mechanism Of Clearing Damp Turbidity And Stasis Treatment For Non-alcoholic Fatty Liver Based On IRE1?/JNK Signaling Pathway

Objective:To observe the effect of Modifide Yinshao powder,a traditional Chinese herbal medicine for clearing damp turbidizing and resolving stasis,on blood lipids,insulin resistance,liver function,liver pathology and endoplasmic reticulum stress-insulin resistance in nonalcoholic fatty liver disease(NAFLD)rats IRE la/JNK signaling pathways to explore the mechanism of treatment of non-alcoholic fatty liver.Method:?Modeling and grouping:60 male SD rats weighing 200g ± 20g were randomly divided into normal diet group and high-fat diet group.The high-fat diet group was given a high fat diet of 10%lard + 2%cholesterol + 0.5%sodium cholate + 5%egg yolk powder +normal diet for 8 weeks.After 8 weeks,the high-fat diet group were randomly divided into model group,Yishanfu group,traditional Chinese medicine high-dose group,traditional Chinese medicine Medium-dose group and low-dose Chinese medicine group,each group of 10.? Therapeutic administration:From the 9th week,the rats in the Yishanfu group and the traditional Chinese medicine group were given Yishanfu and Modifide Yinshao powder respectively,and were given gavage daily for 6 weeks.?Detection of indicators:After treatment,the blood of rats was collected to detect ALT,AST,TG,TC,HDL-C,LDL-C,FFA,TBIL,IBIL,DBIL,FPG and FINS.Liver Index and Insulin Resistance Index(HOMA-IR)were calculated.The rat liver tissue was taken after dissection,and the red blood O staining was performed to observe the pathological changes of the liver tissue in each group.PCR was used to detect the expression of m RNA of IRE la.The expression of IRE1?and JNK1 protein and the phosphorylation level of IRS 1(Ser307)were detected by Western-blot.Result:1.Compared with the model group,the body weight,liver wet weight and liver index in each treatment group decreased significantly(P<0.05),the liver wet weight and liver index in the high-dose group of traditional Chinese medicine were significantly lower than that of other treatment' groups(P<0.05).2.Oil red O staining results showed that,compared with the model group,the lipid accumulation area of each treatment group was significantly reduced(P<0.05);Between the treatment groups,the cumulative area of lipid droplets in each treatment group of traditional Chinese medicine was lower than that of Yishanfu group;The cumulative area of lipid droplets in the high-dose Chinese medicine group,the medium-dose Chinese medicine group,and the low-dose Chinese medicine group showed an increasing trend(P<0.05).3.The results of PCR and Western-blot showed that compared with the model group,the mRNA expression of IREl?,the expression of IRE1? and JNK 1 protein and the phosphorylation of IRS1(Ser307)in each treatment group were significantly decreased(P<0.05)Among the treatment groups,the expression level of m RNA in the IRE1? of the Chinese traditional Chinese medicine dose group was significantly lower than that in the YiShanfu group(P<0.05).The m RNA expression level of IRE1? in high-dose group,medium-dose group and low-dose group of traditional Chinese medicine showed increasing trend(P<0.05).The expression levels of IRE1??JNK1 protein,and IRS1(Ser307)phosphorylation in the high-dose Chinese traditional medicine group were significantly reduced,and were significantly different from the other treatment groups(P<0.05).Conclusion:1.The Modifide Yinshao powder which was base on clearing damp turbidizing and resolving stasis can improve NAFLD lipid metabolism disorder,lower blood levels of FFA,TG,TC,HDL-C,LDL-C,and can be reduced by blood glucose and insulin Levels,improve insulin resistance(IR),and improve the excessive deposition of lipids in the liver.2.The Modifide Yinshao powder which was base on clearing damp turbidizing and resolving stasis can improve NAFLD rat liver function,reduce blood levels of ALT,AST,TBIL,IBIL,DBIL,play an antioxidant and cytoprotective effect,protect liver function,Delay the progress of liver injury.3.The method of clearing damp turbidizing and resolving stasis by Modifide Yinshao powder can inhibit the expression of IRE1?m RNA.the expression of IRE1? and JNK1 protein and the expression of IRS1(Ser307)phosphorylation level by affecting the IREla/JNK signaling pathway in endoplasmic reticulum stress-insulin resistance,thereby reversing the degree of non-alcoholic fatty liver.4.The method of clearing damp turbidizing and resolving stasis by Modifide Yinshao powder treatment of NAFLD was better than Yishanfu of western medicine,and traditional Chinese medicine treatment effect of high dose of traditional Chinese medicine was best.