槲皮素对大鼠非酒精性脂肪肝炎的治疗作用及其机制

摘要

目的 观察槲皮素对大鼠非酒精性脂肪肝炎(NASH)的治疗作用,以及槲皮素对NASH大鼠肝组织核因子-κB (NF-κB)及其下游转录因子表达水平的影响.方法 采用高脂饲料喂食6周,建立NASH大鼠模型.灌胃给予40～160 mg/kg槲皮素治疗4周.采用生化检测仪检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平.采用Western blotting法检测各组肝脏中NF-κB蛋白表达情况.采用RT-PCR技术检测各组肝脏中肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)和白细胞介素1β(IL-1β) mRNA的表达情况.结果 与高脂模型组相比,槲皮素各剂量组大鼠血清LDL-C、TC、AST水平显著降低.病理组织学检查结果表明,给予槲皮素治疗后,可明显减轻NASH大鼠肝脏脂肪变性和炎性细胞浸润;同时,还可明显降低TNF-o、IL-6和IL-1β mRNA以及NF-κBp65蛋白的表达,并呈一定的量效关系.结论 槲皮素对高脂饮食诱导大鼠NASH有明显治疗作用,作用机制可能与其抑制肝细胞脂质沉积和调控NF-κB通路有关.%Objective To investigate the therapeutic effects of quercetin on non-alcoholic steatohepatitis (NASH) in rats,and the effects of quercetin on expressions of nuclear factor-κB (NF-κB).Methods The rats were fed with a high-fat diet for 6 weeks to induce NASH.The NASH model rats were given by gavage with quercetin 40-160 mg/kg for 4 weeks.The levels of serum total cholesterol (TC),triglycer ides (TG),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C),alanine aminotransferase (ALT),and aspartate aminotransferase (AST) were measured by the automatic blood chemical analyzer.The protein expressions of NF-κB in the hepatic tissues were detected by western blotting while tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and interleukin-1 β (IL-1 β) mRNA by RT-PCR.Results Compared with control groups,the serum levels of LDL-C,TC and AST were decreased significantly in the quercetin-treated groups.Oral administration of quercetin improved hepatic steatosis and inflammatory cell infiltration effectively in NASH rats,reduced the mRNA expressions of TNF-α,IL-6 and IL-1β,and down-regulated the protein expression of NF-κB,with a dose-dependent trend which can be observed.Conclusion Quercetin had significant therapeutic benefits to prevent NASH through inhibiting hepatic lipid accumulation,that may be works through regulating NF-κB pathway.