实验动物与比较医学 ›› 2017, Vol. 37 ›› Issue (2): 83-88.DOI: 10.3969/j.issn.1674-5817.2017.02.001

• 论著 •    下一篇

槲皮素对大鼠非酒精性脂肪肝炎的治疗作用及其机制

李剑波1,2, 余陈欢3, 王志远3, 方杰3, 应华忠3   

  1. 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
  • 收稿日期:2016-11-21 出版日期:2017-04-25 发布日期:2017-04-25
  • 作者简介:李剑波(1985-),男,硕士研究生,研究方向:降脂中药药理学。E-mail:15356189099@163.com
  • 基金资助:
    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)

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

LI Jian-bo1,2, YU Chen-huan3, WANG Zhi-yuan3, FAN Jie3, YING Hua-zhong1   

  1. 1. College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China;
    2. Pharmacy Department, Yuhang First People's Hospital, Hangzhou 310018, China;
    3. Zhejiang Laboratory Animal Centre, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China
  • Received:2016-11-21 Online:2017-04-25 Published:2017-04-25

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。

关键词: 槲皮素, 非酒精性脂肪肝炎(NASH), NF-κB, 炎症反应, 高血脂

Abstract: 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.

Key words: Quercetin, Non-alcoholic steatohepatitis (NASH), Nuclear factor-κB (NF-κB), Inflammation, Hyperlipoidemia

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