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作 者:邢菊玲 刘芬 冯萌 郝梦娇 黄天来 周欣欣[1] 汤湘江 XING Juling;LIU Fen;FENG Meng;HAO Mengjiao;HUANG Tianlai;ZHOU Xinxin;TANG Xiangjiang(School of TCM,Guangzhou University of TCM,Guangzhou 510006,China;School of Pharmacy,Sun Yat-sen University,Guangzhou 510275,China;Dept.of Neurology,Guangdong Provincial Hospital of TCM/University Town Hospital,the Second Affiliated Hospital of Guangzhou University of TCM,Guangzhou 510006,China)
机构地区:[1]广州中医药大学中药学院,广州510006 [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
出 处:《中国药房》2021年第15期1868-1873,共6页China Pharmacy
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(10μmol/L)和桑根酮C低、中、高浓度组(2、4、8μmol/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。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(10μmol/L),sangerone C low,medium and high concentration groups(2,4,8μmol/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-1αin 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-1αwere 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 PPARαpathway 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 PPARαsignaling pathway,improving cell lipid oxidation ability and inhibiting lipid synthesis.
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