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桑根酮C对游离脂肪酸诱导人肝癌HepG2细胞脂质蓄积的改善

        作用


        邢菊玲 ,刘 芬 ,冯 萌 ,郝梦娇 ,黄天来 ,周欣欣 ,汤湘江 (1.广州中医药大学中药学院,广州 510006;
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               1*
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                        1
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        2.中山大学药学院,广州 510275;3.广东省中医院/广州中医药大学第二附属医院大学城医院神经内科,广州
        510006)
        中图分类号 R965          文献标志码 A           文章编号 1001-0408(2021)15-1868-06
        DOI   10.6039/j.issn.1001-0408.2021.15.13
        摘   要   目的:研究桑根酮C对游离脂肪酸诱导的人肝癌HepG2细胞脂质蓄积的改善作用。方法:将HepG2细胞分为对照组、模
        型组、非诺贝特组(10 μmol/L)和桑根酮C低、中、高浓度组(2、4、8 μmol/L),除对照组外,其余各组细胞加入1 mmol/L游离脂肪酸
        以诱导建立脂质蓄积模型,且各给药组加入相应含药培养基进行培养。采用油红O染色法观察细胞中脂质蓄积情况,并测定脂质
        水平和三酰甘油(TG)含量;采用实时荧光定量聚合酶链式反应法和 Western blot 法检测细胞中过氧化物酶体增殖物激活受体α
        (PPARα)、肉碱棕榈酰转移酶1(CPT-1)、成脂甾醇元件结合蛋白固醇调节元件结合蛋白1c(SREBP-1c)、脂肪酸合成酶(FAS)、沉
        默信息调节因子1(SIRT1)、过氧化物酶体增殖物激活受体γ辅助激活物1α(PGC-1α)的mRNA和蛋白表达水平。结果:与对照组
        比较,模型组细胞核明显萎缩、体积变小,脂滴数明显增加;细胞中脂质水平、TG含量以及SREBP-1c、FAS 的mRNA和蛋白表达水
        平均显著升高(P<0.05 或 P<0.01),PPARα、CPT-1、SIRT1、PGC-1α 的 mRNA 和蛋白表达水平均显著降低(P<0.01)。与模型组
        比较,桑根酮C各浓度组细胞核萎缩不明显、体积大小正常,脂滴数明显减少;细胞中脂质水平、TG含量以及上述PPARα通路相关
        基因的mRNA和蛋白(桑根酮C低浓度组的SREBP-1c蛋白除外)表达水平均显著逆转(P<0.05或P<0.01)。结论:桑根酮C可改
        善HepG2细胞的脂质蓄积;其作用机制可能与调节PPARα信号通路、提高细胞脂质氧化能力、抑制脂质合成有关。
        关键词 桑根酮C;HepG2细胞;脂质蓄积;PPARα信号通路
        Improvement Effects of Sanggenone C on Lipid Accumulation in FFA-induced Human Liver Cancer
        HepG2 Cells
        XING Juling ,LIU Fen ,FENG Meng ,HAO Mengjiao ,HUANG Tianlai ,ZHOU Xinxin ,TANG Xiangjiang         3
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                    1
        (1. School of TCM,Guangzhou University of TCM,Guangzhou 510006,China;2. School of Pharmacy,Sun
        Yat⁃sen University,Guangzhou 510275,China;3. Dept. of Neurology,Guangdong Provincial Hospital of TCM/
        University Town Hospital,the Second Affiliated Hospital of Guangzhou University of TCM,Guangzhou
        510006,China)
        ABSTRACT    OBJECTIVE:To study the improvement effects of sanggenone C on lipid accumulation in human liver cancer
        HepG2 cells induced by free fatty acid (FFA). METHODS:HepG2 cells were divided into control group,model group,
        fenofibrate group(10 μmol/L),sangerone C low,medium and high concentration groups(2,4,8 μmol/L). Except for control
        group,other groups were treated with 1 mmol/L FFA to induce lipid accumulation model,and administration groups were cultured
        with relevant medium containing drugs. The lipid accumulation was observed by oil red O staining,and lipid level and triglyceride
        (TG) content were also determined. Real-time PCR and Western blot assay were adopted to detect the mRNA and protein
        expression of PPARα,CPT-1,SREBP-1c,FAS,SIRT1 and PGC-1α in HepG2 cells. RESULTS:Compared with control group,
        the nucleus was atrophied significantly and the volume became smaller,and the number of lipid droplets was significantly
        increased;the level of lipid,TG content,mRNA and protein expression of SREBP-1c and FAS were significantly increased(P<
        0.05 or P<0.01),mRNA and protein expression of PPARα,CPT-1,SIRT1 and PGC-1α were decreased significantly(P<0.01).
        Compared with model group,no obvious nucleus atrophy and normal volume were observed in sangerone C groups,and the
        number of lipid droplets was significantly reduced;the levels of lipid,TG content,mRNA and protein expression of PPAR α
        pathway related genes(except for SREBP-1c protein in saggenone C low concentration group)were significantly reversed(P<
        0.05 or P<0.01). CONCLUSIONS:Sangenone C can significantly improve the lipid accumulation of HepG2 cells,and its
                                                            mechanism may associated with regulating PPAR α signaling
            * 硕 士 研 究 生 。 研 究 方 向 :中 药 内 分 泌 药 理 学 。 E-mail:  pathway,improving cell lipid oxidation ability and inhibiting
        15562591483@163.com                                 lipid synthesis.
            # 通信作者:副教授,硕士生导师。研究方向:中药新药与开发。                  KEYWORDS     Sanggenone C;HepG2 cells;Lipid accumu-
        E-mail:yanchengys@163.com                           lation;PPARα signaling pathway


        ·1868 ·  China Pharmacy 2021 Vol. 32 No. 15                                 中国药房    2021年第32卷第15期
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