Influence of quercetin on expressions of stearyl coenzyme A saturated enzyme 1 and liver X receptorαin nonalcoholic fatty liver disease model rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the role of stearyl coenzyme A saturated enzyme 1 (SCD1) and liver X receptorα(LXR-α) in the pathogegnesis of nonalcoholic fatty liver disease (NAFLD) of rats and influence of quercetin on them. METHODS Fifty-six male rats were randomly divided into normal control group (n=16) and model group (n=40). The normal control group was fed with a common diet and the model group was fed with a high fat diet. After 8 weeks, 8 rats from each group were killed. The hepatic tissue of rats showed vast cell fatty degeneration and inflammatary cell infiltration, suggesting that the rat NAFLD model was successfully established. The model group was further divided into four groups quercetin 75, 150 and 300 mg · kg-1 treatment groups (ig, once daily) for 4 weeks and model group. After 4 weeks, serum levels of glutamate pyruvic transaminase (GOT), glutamic oxaloacetic transaminase (GPT), total cholesterol (TC) and trigluceride (TG) were detected. Pathological changes of hepatic tissues were deteceted by HE staining. The protein levels of SCD1 and LXR-αwere detected by immunohistochemistry and the mRNA levels of SCD1 and LXR-α were quantified by reverse tran-scription quantitative polymerase chain reactin (RT-qPCR). The protein levels of LXR-αwere tested by Western blotting. RESULTS At the end of 8 weeks, compared with normal control group, the body mass of rats in model group was increased markedly (P<0.05), fat drops were visible in hepatocyte cells, different levels of inflammatory cells and necrosis were detected and the levels of GOT, GPT, TC and TG increased markedly (P<0.05). At the end of 12 weeks, compared with model group, the body mass of rats in each quercetin treatment group decresed (P<0.05), the steatosis score and inflam-matary score of quercetin 150 and 300 mg · kg-1 treatment groups decreased (P<0.05, P<0.01). The levels of GOT, GPT, TC and TG in quercetin 300 mg · kg-1 treatment groups were decresed (P<0.05), but were higher than in the control group. lmmunohistochemical results showed the protein expression of SCD1 in quercetin 150 and 300 mg·kg-1 treatment groups was increased (P<0.05, P<0.01) but the expression of LXR-α protein in quercetin 300 mg · kg-1 treatment groups was decreased (P<0.05). RT-qPCR results showed that the mRNA level of SCD1 in each quercetin treatment group was increased (P<0.01) and the mRNA level of LXR-αin quercetin 150 and 300 mg · kg-1 treatment groups was decreased (P<0.05, P<0.01). Western blotting results showed that the protein expression of LXR-α in each quercetin treatment group was decreased (P<0.01). CONCLUSION Quercetin has therapeutic effect on NAFLD rats and the mechanism may be related to the increase of SCD1 expression and the decrease of LXR-α expression.