槲皮素对大鼠非酒精性脂肪肝炎的治疗作用及其机制  

Therapeutic Effects and Mechanisms of Quercetin on Non-alcoholic Steatohepatitis in Rats

作　　者：李剑波[1,2] 余陈欢[3] 王志远[3] 方杰[3] 应华忠[3] LI Jian-bo YU Chen-huan WANG Zhi-yuan FAN Jie YING Hua-zhong(College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China Pharmacy Department, Yuhang First People＇s Hospital, Hangzhou 310018, China Zhejiang Laboratory Animal Centre, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China)

机构地区：[1]浙江中医药大学药学院,杭州310053 [2]杭州市余杭区第一人民医院药剂科,杭州311000 [3]浙江省医学科学院浙江省实验动物与安全性研究重点实验室,杭州310013

出　　处：《实验动物与比较医学》2017年第2期83-88,共6页Laboratory Animal and Comparative Medicine

基　　金：国家自然科学基金面上项目(81573591);浙江省自然科学基金重点项目(LZ17H280001);浙江省省属科研院所专项计划项目(2014F10033)

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-α、IL-6和IL-1β mRNA以及NF-κB p65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）, triglycerides （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- 1β （IL- 1β） 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.

关 键 词：槲皮素非酒精性脂肪肝炎 (NASH)NF-κB 炎症反应 高血脂 

分 类 号：R285.5[医药卫生—中药学]