Effect of Zequ Mingshan Compound Prescription(泽曲明山复方)on Mouse Model of Non-alcoholic Steatohepatitis
Objective Zequ Mingshan Compound Prescription(泽曲明山复方)is an empirical formula for the clinical treat-ment of metabolic associated fatty liver disease(MAFLD).This study explored the impact of this empirical formula on the rat model of non-alcoholic steatohepatitis(NASH)and its possible mechanisms.Method SD rats were given choline deficient high fat diet(CDHF diet)for 8 weeks to establish a NASH model.The rats were randomly divided into model group,low and high dose groups of traditional Chinese medicine and Shuilinjia group.The model was established and the corresponding drug interven-tion was provided.The choline rich high fat diet(CSHF diet)was as the control group.The effects of corresponding drugs on ser-um biochemistry,liver pathology,PI3 K-AKT-mTOR signaling pathway mRNA and protein expression in model rats were com-pared.Results(1)Body weight and liver/body weight:There was no statistically significant difference in body weight among the 5 groups.The liver/body weight of the rats of the model group significantly increased,while the liver/body weight of the rats of each intervention group decreased to varying degrees.The high-dose group had the most significant therapeutic effect.(2)Liver function and blood lipids:Compared with those of the control group,the serum levels of alaninetransaminase(ALT),glutamic oxa-loacetic transaminase(AST),triglyceride(TG),total cholesterol(TC)and low density lipoprotein cholesterol(LDL-C)of the model group were significantly increased.The liver function and blood lipids of rats in each intervention group decreased to var-ying degrees,with the high-dose group having the most significant therapeutic effect.(3)Liver pathology:HE staining showed a large number of fat vacuoles and inflammatory cell infiltration in the cytoplasm of the liver of the model group rats.Sirius red stai-ning showed a large amount of fibrous tissue deposition in the central vein,confirming the validity of the model.Each intervention group showed varying degrees of improvement in liver HE and Sirius red staining,with the high-dose group showing the most sig-nificant improvement.(4)Effect on the mRNA expressions of SREBP-1 and LDLR in liver tissue:Compared with the control group,the model group showed a significant increase in SREBP-1 mRNA expression.Each intervention group showed varying degrees of down-regulation,with the high-dose group being the most significant.Compared with those in the control group,the expression of LDLR mRNA in the model group decreased significantly.The expression levels increased to varying degrees in each intervention group,with the high-dose group showing the most significant improvement.(5)Effect on the expressions of SREBP-1 and LDLR proteins in liver tissue:Compared with those of the control group,the SREBP-1 protein staining in the liv-er tissue of the model group rats was deeper,and the staining in each intervention group was lighter than that in the model group.Among them,the effect of the traditional Chinese medicine group was more significant.Compared with that of the control group,the LDLR protein staining in the liver tissue of the model group was shallow,while the staining in each intervention group was deeper than that in the model group.Among them,the high-dose group had a more significant effect.(6)The effect on the ex-pressions of PI3K,mTOR and AKT proteins in liver tissue:Through immunofluorescence staining observation,the fluorescence signal expression of the sample cells in the model group was bright and unevenly distributed.The fluorescence signal expression in the control group was dim.The fluorescence signal expression brightness of each intervention group was down-regulated com-pared to that of the model group and the improvement was more significant in the traditional Chinese medicine intervention group.Conclusion Zequ Mingshan Compound Prescription may alleviate liver inflammation,reduce hepatic production and accumula-tion,improve NASH by regulating the PI3 K/AKT/mTOR pathway and exhibit dose-dependent effects during treatment.