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纸质出版日期:2021,
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邢菊玲, 刘芬, 冯萌, 等. 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[J]. 中国药房, 2021,32(15).
XING Juling, LIU Fen, FENG Meng, et al. Improvement Effects of Sanggenone C on Lipid Accumulation in FFA-induced Human Liver Cancer HepG 2 Cells[J]. China Pharmacy, 2021,32(15).
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1mmol/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Westernblot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 ef fects 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 PPARα 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 HepG 2 cells,and its mechanism may associated with regulating PPAR α signaling pathway,improving cell lipid oxidation ability and inhibiting lipid synthesis.
桑根酮CHepG2细胞脂质蓄积PPARα信号通路
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