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.%目的 探讨硬脂酰辅酶A去饱和酶1(SCD1)和肝X受体α(LXR-α)在大鼠非酒精性脂肪肝(NAFLD)发病机制中的作用及槲皮素对SCD1和LXR-α表达的影响.方法 56只雄性SD大鼠随机分为正常对照组(16只)和高脂组(40只),分别予以普通饲料或高脂饲料喂养.8周后,正常对照组和高脂组各取8只大鼠,肝组织HE染色出现大量肝细胞脂肪变性及炎症细胞浸润,确认NAFLD造模成功.将NAFLD组(32只)进一步随机分为NAFLD模型组及槲皮素75,150和300 mg·kg-1治疗组(1次·d-1,ig).4周后,测血液谷丙转氨酶(GPT)、谷草转氨酶(GOT)、总胆固醇(TC)和甘油三脂(TG)水平;取肝组织进行HE染色观察病理变化;免疫组化检测SCD1和LXR-α蛋白表达水平;实时定量逆转录聚合酶链式反应(RT-qPCR)检测SCD1和LXR-α的mRNA水平;Western蛋白印迹法检测LXR-α蛋白水平.结果 与正常对照组比较,第8周未,高脂组大鼠体质量显著增加(P<0.05),肝细胞内可见大量脂滴,并出现了不同程度的炎症细胞浸润和坏死,血清GOT,GPT,TC和TG水平明显升高(P<0.05);第12周末,SCD1 mRNA和蛋白表达减少(P<0.01),LXR-αmRNA和蛋白表达增高(P<0.01).与NAFLD模型组比较,各槲皮素治疗组大鼠12周末体质量明显减轻(P<0.05),槲皮素150和300 mg·kg-1治疗组大鼠脂肪变性评分和炎症程度评分降低(P<0.05,P<0.01),血清GOT,GPT,TC和TG水平降低(P<0.01),SCD1蛋白表达增加(P<0.05).结论 槲皮素对高脂饮食诱导的NAFLD大鼠有治疗作用,其机制与SCD1表达增加和LXR-α表达降低有关.
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