二甲双胍对人肝细胞Huh7脂质蓄积的影响及作用机制
作者:
作者单位:

(南华大学心血管疾病研究所 动脉硬化学湖南省重点实验室 湖南省动脉硬化性疾病国际科技创新合作基地 衡阳医学院,湖南省衡阳市 421001)

作者简介:

郑洁,硕士研究生,研究方向为动脉粥样硬化病因发病学与防治基础,E-mail为441311759@qq.com。通信作者唐志晗,教授,博士研究生导师,研究方向为动脉粥样硬化病因发病学与防治基础,E-mail为tangzhihan98@163.com。

基金项目:

湖南省科技计划项目(2015JC3081)


Effect and mechanism of metformin on lipid accumulation in Huh7 hepatocytes
Author:
  • ZHENG Jie

    ZHENG Jie

    Institute of Cardiovascular Disease & Key Laboratory for Arteriosclerology of Hunan Province& Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease & Hengyang Medical College, University of South China, Hengyang, Hunan 421001
    在知网中查找
    在百度中查找
    在本站中查找
  • TANG Zhihan

    TANG Zhihan

    Institute of Cardiovascular Disease & Key Laboratory for Arteriosclerology of Hunan Province& Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease & Hengyang Medical College, University of South China, Hengyang, Hunan 421001
    在知网中查找
    在百度中查找
    在本站中查找
Affiliation:

Institute of Cardiovascular Disease & Key Laboratory for Arteriosclerology of Hunan Province& Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease & Hengyang Medical College, University of South China, Hengyang, Hunan 421001)

  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • | |
    摘要:

    目的 研究二甲双胍对肝细胞脂质蓄积的影响及作用机制。方法 体外培养人源Huh7肝细胞,细胞随机分为空白对照组及5 mmol/L二甲双胍、10 mmol/L二甲双胍、15 mmol/L二甲双胍处理组,确定最佳浓度后,使用LDL荷脂,然后分为空白对照组、LDL处理组和LDL+15 mmol/L二甲双胍处理组。实验终点,采用细胞增殖及毒性检测试剂盒检测细胞存活率,油红O染色和BODIPY脂质探针检测细胞内脂质含量,Dil-LDL检测细胞脂质摄取能力,Western blot分析固醇调节元件结合蛋白2(SREBP-2)、SREBP-1c、低密度脂蛋白受体(LDLR)和前蛋白转化酶枯草溶菌素9(PCSK9)蛋白的表达情况。结果 二甲双胍可抑制LDL诱导的肝细胞脂质蓄积,降低SREBP-2、SREBP-1c、LDLR和PCSK9的蛋白表达。结论 二甲双胍可能通过减少转录因子SREBP-2和SREBP-1c,下调LDLR表达,从而抑制细胞脂质蓄积。

    Abstract:

    Aim To investigate the effect and mechanism of metformin on lipid accumulation in Huh7 hepatocytes. Methods Huh7 cells were cultured in vitro and divided into:blank control group, 5 mmol/L, 10 mmol/L and 15 mmol/L metformin treatment group. After determing the optimal concentration, LDL was used to load fat, and then divided into:blank control group, LDL group, LDL+15 mmol/L metformin treatment group. Cell proliferation and toxicity test kits were used to detect cell survival rate, oil red O and BODIPY lipid probes were used to detect intracellular lipid content, Dil-LDL was used to detect cell lipid uptake capacity, and Western blot analysis was performed on sterol regulatory element binding protein-2 (SREBP-2), sterol regulatory element binding protein-1c (SREBP-1c), low density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin 9 (PCSK9) protein expression. Results Metformin can inhibit LDL-induced lipid accumulation in Huh7 hepatocytes and reduce protein expression of SREBP-2, SREBP-1c, LDLR, and PCSK9. Conclusion Metformin reduces intracellular lipid uptake by reducing LDLR expression and inhibiting the expression of the transcription factors SREBP-2 and SREBP-1c.

    参考文献
    [1] 中国研究型医院学会肝病专业委员会, 中国医师协会脂肪性肝病专家委员会, 中华医学会肝病学分会脂肪肝与酒精性肝病学组, 等.脂肪性肝病诊疗规范化的专家建议(2019年修订版).临床肝胆病杂志, 9,5(11):2426-2430.
    [2] Li J, Zou B, Yeo YH, et al.Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019:a systematic review and meta-analysis.Null, 9,4(5):389-398.
    [3] Kothari S, Dhami-Shah H.Antidiabetic drugs and statins in nonalcoholic fatty liver disease.J Clin Exp Hepatol, 9,9(6):723-730.
    [4] Tang X, Li J, Xiang W, et al.Metformin increases hepatic leptin receptor and decreases steatosis in mice.J Endocrinol, 6,0(2):227-237.
    [5] 陈思, 赵金珍, 胡晶, 等.他汀类药物在治疗非酒精性脂肪肝病中的研究进展.中国动脉硬化杂志, 7,5(3):297-303.
    [6] Kita Y, Takamura T, Misu H, et al.Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.PLoS One, 2,7(9):e43056.
    [7] Sharma A, Bandyopadhayaya S, Chowdhury K, et al.Metformin exhibited anticancer activity by lowering cellular cholesterol content in breast cancer cells.PLoS One, 9,4(1):e0209435.
    [8] Zhang F, Sun W, Chen J, et al.SREBP-2, a new target of metformin?.Drug Des Devel Ther, 8,2:4163-4170.
    [9] Jiang X, Yu J, Wang X, et al.Quercetin improves lipid metabolism via SCAP-SREBP2-LDLR signaling pathway in early stage diabetic nephropathy.Diabetes Metab Syndr Obes, 9,2:827-839.
    [10] Liu J, Jin X, Yu CH, et al.Endoplasmic reticulum stress involved in the course of lipogenesis in fatty acids-induced hepatic steatosis.J Gastroenterol Hepatol, 0,5(3):613-618.
    [11] Min QQ, Qin LQ, Sun ZZ, et al.Effects of metformin combined with lactoferrin on lipid accumulation and metabolism in mice fed with high-fat diet.Nutrients, 8,0(11).DOI:10.3390/nu111628.
    [12] Zarei M, Pujol E, Quesada-López T, et al.Oral administration of a new HRI activator as a new strategy to improve high-fat-diet-induced glucose intolerance, hepatic steatosis, and hypertriglyceridaemia through FGF21.Br J Pharmacol, 9,6(13):2292-2305.
    [13] Tang ZH, Li TH, Peng J, et al.PCSK9:A novel inflammation modulator in atherosclerosis?.J Cell Physiol, 9,4(3):2345-2355.
    [14] Li HH, Li J, Zhang XJ, et al.3,4-Dihydrocucurbitacin B promotes lipid clearance by dual transcriptional regulation of LDLR and PCSK9.Acta Pharmacol Sin, 0,1(3):327-335.
    引证文献
引用本文

郑洁,唐志晗.二甲双胍对人肝细胞Huh7脂质蓄积的影响及作用机制[J].中国动脉硬化杂志,2020,28(5):429~434.

复制
分享
文章指标
  • 点击次数:633
  • 下载次数: 925
历史
  • 收稿日期:2019-10-16
  • 最后修改日期:2020-03-09
  • 在线发布日期: 2020-05-26