维生素C和E对瘦素诱导的肝星状细胞增殖与TIMP-1上调的抑制作用

目的观察维生素C和E对瘦素诱导肝星状细胞(hepatic stellate cell,HSC)的增殖及组织抑制基质金属蛋白酶-1(tissue inhibitor of matrix metalloproteinase-1,TIMP-1)上调的影响。方法培养人HSC,按照分组加入瘦素和(或)不同浓度的维生素C和E。磺基罗丹明B法检测HSC增殖,活性氧(ROS)检测探针2,7-二氯二氢荧光素二乙酯检测ROS,酶联免疫吸附实验测定TIMP-1的浓度。结果维生素C为100、200、400μmol/L时抑制瘦素诱导的HSC增殖效果和瘦素组比较差异有统计学意义(P<0.05),维生素E为80、160、320μmol/L时与溶媒瘦素组比较差异有统计学意义(P<0.05)。最高浓度联合后,抑制瘦素诱导的HSC增殖效果更明显(P<0.05)。同时上述浓度均能抑制瘦素诱导的ROS产生(P<0.05),抑制瘦素诱导的TIMP-1产生(P<0.05),最高浓度联合组抑制TIMP-1效果较单独用药时明显(P<0.05)。结论抗氧化剂维生素E和C可能通过抑制瘦素诱导的氧化应激,抑制HSC增殖以及TIMP-1的产生。

Vitamins C and E suppress leptin-induced proliferation and TIMP-1 upregulation in hepatic stellate cells

Objective To determine the effect of vitamins E and C on the proliferation and increased expression of tissue inhibitor of matrix metalloproteinase-1(TIMP-1) in hepatic stellate cells(HSCs) induced by leptin.Methods Human HSCs were cultured,and then treated in precent or absent of leptin and/or vitamin C and E at different concentrations.Sulforhodamine B assay was performed to test proliferation of HSCs,the detection probe of reactive oxygen species(ROS) 2,7-dichlorfluorescein-diacetate was used to detect ROS,and enzyme-linked immunosorbent assay was to detect concentration of TIMP-1.Results Vitamin C at concentrations of 100,200 and 400 μmol/L resulted in statistical inhibition of proliferation of HSC induced by leptin compared with leptin group(P<0.05),so did vitamin E at concentrations of 80,160 and 320 μmol/L(P<0.05).Combined the 2 agents at the highest concentrations had more inhibitory effect on HSC proliferation induced by leptin than they used alone(P<0.05).At the same time,all the concentration groups resulted in significant inhibition in ROS and TIMP-1 productions induced by leptin(P<0.05).Compared with single group,the highest concentrations combined group had more inhibitory effect in ROS and TIMP-1 productions(P<0.05).Conclusion Anti-oxidant vitamins E and C may inhibit the proliferation and TIMP-1 production of HSCs by inhibiting oxidative stress induced by leptin.