沙苑子苷A对脂肪变L02细胞中三酰甘油水解及炎症介质的影响  

Effect of Complanatoside A on ATGL,PPARs, and Inflammatory Factors of Steatosis L02 Cells

作　　者：高晶[1] 魏益谦 孟智睿 邵紫萱 李丽[1] 张建军[1] 王景霞[1] GAO Jing;WEEI Yiqian;MENG Zhirui;SHAO Zixuan;LI Li;ZHANG Jianjun;WANG Jingxia(Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京100029

出　　处：《世界中医药》2022年第17期2437-2442,共6页World Chinese Medicine

基　　金：国家自然科学基金项目(81673617)——雌激素受体介导的沙苑子温阳化浊调节肝脏TG代谢的机制研究。

摘　　要：目的:研究沙苑子苷A对脂肪变L02细胞的降脂效果和作用机制。方法:采用游离脂肪酸(FFA)诱导肝L02细胞脂肪变性,分为对照组、模型组、沙苑子苷A低剂量、中剂量、高剂量组(1μmol/L、10μmol/L、50μmol/L),流式细胞仪检测细胞凋亡和脂肪堆积,按照试剂盒检测三酰甘油(TG)、胆固醇(TC)、丙二醛(MDA)、超氧化物歧化酶(SOD)的水平,实时荧光定量PCR(qPCR)检测三酰甘油水解酶(ATGL)、过氧化物酶体增殖物激活受体α(PPAR-α)、过氧化物酶体增殖物激活受体γ(PPARγ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)mRNA的表达,蛋白质印迹法(Western Blotting)检测ATGL、PPAR-α、PPARγ、TNF-α、IL-6蛋白的表达。结果:沙苑子苷A能显著减少脂肪堆积,降低TG、TC、MDA含量,增加SOD活性,降低细胞凋亡率,减轻脂毒性造成的肝细胞损伤,与模型组比较差异有统计学意义(P<0.05,P<0.01);沙苑子苷A能升高ATGL、PPAR-α、PPARγmRNA和蛋白的表达,同时降低TNF-α、IL-6 mRNA和蛋白的表达,与模型组比较差异有统计学意义(P<0.01)。结论:沙苑子苷A可能通过上调PPARα、PPARγ的表达,使ATGL表达增加,促进肝脏TG的水解,减少肝脏脂肪的沉积,缓解氧化应激,抑制TNF-α和IL-6的分泌,减轻炎症反应,从而恢复肝细胞的正常功能。Objective:To study the hypolipidemic effect of complanatoside A on steatosis L02 cells and the mechanism.Methods:Free fatty acid(FFA) was used to induce steatosis in human liver L02 cells.The cells were classified into the blank group, model group, and low-dose, medium-dose, and high-dose complanatoside A groups(1 μmol/L,10 μmol/L,and 50 μmol/L,respectively).Apoptosis and fat accumulation were detected by flow cytometry.The levels of triglyceride(TG),total cholesterol(TC),malondialdehyde(MDA),and superoxide dismutase(SOD) were determined with corresponding kits.The mRNA expression of adipose triglyceride lipase(ATGL),peroxisome proliferator-activated receptor(PPAR)-α,PPAR-γ,tumor necrosis factor(TNF)-α,and interleukin-6(IL-6) was measured by qPCR,and the protein expression of ATGL,PPAR-α,PPARγ,TNF-α,and IL-6 by Western Blotting.Results:Complanatoside A reduced fat accumulation, content of TG,TC,and MDA,and apoptosis rate, enhanced SOD activity, and alleviated liver cell injury caused by lipotoxicity as compared with the model group(P<0.05,P<0.01).Complanatoside A raised the mRNA and protein expression of ATGL,PPAR-α,and PPARγ and lowered the mRNA and protein expression of TNF-α and IL-6 in comparison with the model group(P<0.01).Conclusion:Perhaps by up-regulating the expression of PPAR-α and PPAR-γ,complanatoside A can increase the expression of ATGL,promote the hydrolysis of liver TG,reduce the deposition of fat in liver, alleviate oxidative stress, inhibit the secretion of TNF-α and IL-6,and relieve inflammation, so as to restore the normal function of hepatocytes.

关 键 词：沙苑子 沙苑子苷A 高脂血症 L02细胞 细胞凋亡 三酰甘油 三酰甘油水解酶 过氧化物酶体增殖物激活受体 

分 类 号：R285.5[医药卫生—中药学]