普罗布考抗过氧化氢诱导大鼠血管平滑肌细胞凋亡的初步研究

PREVENTION OF PROBUCOL AGAINST H_2O_2-INDUCED APOPTOSIS IN RAT VASCULAR SMOOTH MUSCLE CELLS

目的 :研究抗氧化剂普罗布考对过氧化氢 (H2 O2 )诱导大鼠血管平滑肌细胞 (VSMC)凋亡的影响。方法 :采用流式细胞术、高效液相色谱分析等方法研究不同浓度H2 O2 作用下细胞内还原型谷胱甘肽(GSH)含量变化与细胞凋亡 ,以及普罗布考抗凋亡作用与细胞内GSH变化的关系。结果 :① 2mmol/LH2 O2使细胞内GSHc含量下降至 0 67μmol/L(P <0 0 1)、细胞凋亡率显著增加 (45 70 % )。②普罗布考加H2 O22mmol/L共同处理后细胞内GSHc含量明显增加 (3 5 3 μmol/L) ,细胞凋亡率显著下降 (2 1 5 9% )。 结论 :2mmol/LH2 O2 使细胞内GSHc含量显著下降 ,VSMC大量凋亡。普罗布考通过维持细胞内氧化还原平衡 ,降低细胞内GSH消耗 ,抑制H2 O2 诱导VSMC凋亡。

Objective:To investigate the effects of probucol on H 2O 2 induced apoptosis in rat VSMC.Methods:Relationship between alteration of intracellular reduced glutathione (GSH) levels and VSMC apoptosis,as well as relation of probucol anti apoptosis of VSMC to the alteration of GSH level were observed by means of flow cytometry,high performance liquid chromatography(HPLC).Results:2mmol/L of H 2O 2 for 6h could result in the substantial decrease in intracellular GSHc levels (0.67μmol/L),with the significant increase in apoptosis rate(45.70%) as compared with control group.When VSMC were incubated with 2mmol/L of H 2O 2 plus 100μmol/L of probucol for 6h,the intracellular GSHc levels markedly resed again (3.53μmol/L, P<0.01), and at the same time,the apoptosis rate greatly declined (21.59, P< 0.05).Conclusion:2mmol/L of H 2O 2 can reduce intracellular GSHc levels and results in a large quantity of VSMC apoptosis.Probucol can protect VSMC against H 2O 2 induced apoptosis via maintaining the equilibrium of intracellular redox status and reducing the depletion of the intracellular GSH.