Hujin Prescription Improves Lipid Metabolism in Mice with Metabolic Associated Fatty Liver Disease by Regulating SIRT1/PGC1α Signaling Pathway
Objective To investigate the therapeutic effect and mechanism of Hujin Prescription on mice with metabolic associated fatty liver disease (MAFLD) based on silent information regulatory I (SIRT1)/peroxisome proliferator-activated receptor γ co-activator 1α(PGC1α)signaling pathway. Methods C57BL/6 mice were randomly divided into six groups:the normal group,the model group,silibinin group(4.8 mg·kg-1),Hujin Prescription high-(21.24 g·kg-1),medium-(10.62 g·kg-1),and low-(5.31 g·kg-1)dose groups. The mice in the normal group were given the basal diet,while the other groups were given high fat diet(HFD)for 10 weeks to replicate the MAFLD animal model. At the beginning of the 11th week,the normal group and the model group were given distilled water by gavage,and the other groups were given corresponding drugs (10 mL·kg-1),once a day for four weeks. The pathological changes of liver tissues were observed using HE and oil red O staining. Biochemical reagent kits were used to detect serum levels of total cholesterol (TC),triglycerides (TG),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C),aspartate aminotransferase (AST),and alanine aminotransferase (ALT). The mRNA and protein expression levels of SIRT1,PGC1α,nuclear respiratory factor 1 (NRF1),and mitochondrial transcription factor A(TFAM)in liver tissues were detected using RT-PCR and Western Blot. Results Compared with the normal group,the body mass,liver mass and liver index of the model group were significantly increased (P<0.01). NAS pathology score and the proportion of lipid droplets area were significantly increased (P<0.01). The serum levels of TC,TG,LDL-C,ALT and AST were significantly increased (P<0.01),but the level of HDL-C was significantly decreased(P<0.01). The mRNA and protein expression levels of SIRT1,PGC1α,NRF1,and TFAM in the liver tissues were significantly decreased (P<0.01). Compared with the model group,the body mass and liver mass of mice in each treatment group were significantly decreased (P<0.01). Moreover,liver index of mice in silibinin group,Hujin Prescription high-and medium-dose groups were significantly decreased (P<0.05,P<0.01). NAS pathology score and the proportion of lipid droplets area were significantly decreased(P<0.05,P<0.01). The serum levels of TG,LDL,ALT and AST of mice in each treatment group were significantly decreased (P<0.05,P<0.01). The serum level of HDL-C of mice in silibinin group,Hujin Prescription low-and high-dose groups was significantly increased(P<0.01),while the serum level of TC of mice in silibinin group and Hujin Prescription high-dose group were significantly decreased (P<0.05,P<0.01). The mRNA expression levels of SIRT1 and TFAM in liver tissues of mice in each treatment group were significantly increased (P<0.01),but the mRNA expression levels of PGC1α and NRF1 in liver tissues of mice in silibinin group,Hujin Prescription medium-and high-dose groups were obviously increased(P<0.05,P<0.01). The protein expression levels of SIRT1 in liver tissues of mice in silibinin group and Hujin Prescription high-dose group were obviously increased(P<0.05,P<0.01). The protein expression levels of PGC1α,NRF1,and TFAM in liver tissues of mice in silibinin group,Hujin Prescription medium-and high-dose groups were obviously increased(P<0.05,P<0.01). Conclusion Hujin Prescription may regulate the SIRT1/PGC1α pathway,affect the biogenesis of liver mitochondria,reduce mitochondrial oxidative stress,promote liver lipid metabolism,and reduce lipid deposition,thus exerting the effect of alleviating MAFLD.
万方数据
维普
