氧化型低密度脂蛋白和α-类脂酸对血管平滑肌细胞中诱生型一氧化氮合酶基因表达的影响

Effects of oxidized low density lipoprotein and α-lipoic acid on expression of inducible nitric oxide synthase mRNA in rat vascular smooth muscle cells

目的 探讨氧化型低密度脂蛋白 (oxidizedlowdensitylipoprotein ,oxLDL)及抗氧化剂α 类脂酸对大鼠血管平滑肌细胞中L 精氨酸 一氧化氮系统的影响。方法 白细胞介素 1β诱导体外培养的血管平滑肌细胞表达诱生型一氧化氮合酶 (induciblenitricoxidesynthase ,iNOS)并产生一氧化氮 ,然后用不同浓度和氧化程度的oxLDL及α 类脂酸进行干预。逆转录 聚合酶链反应法检测血管平滑肌细胞中iNOSmRNA表达量 ,硝酸还原酶法测定一氧化氮含量。结果 oxLDL降低血管平滑肌细胞中iNOSmRNA的表达并减少一氧化氮的产量 ;iNOSmRNA表达及一氧化氮产量与oxLDL的浓度和氧化程度呈负相关 ;预先经α 类脂酸处理后能减轻oxLDL的上述抑制作用。结论 oxLDL显著抑制血管平滑肌细胞中L 精氨酸 一氧化氮系统 ,这一抑制效应与它的浓度和氧化程度有关。α 类脂酸能减轻oxLDL的上述作用。

Objective To investigate the influence of oxLDL and antioxidant α-lipoic acid on L-Arg-NO system in cultured rat aortic VSMC activated by IL-1β.Methods The level of iNOS mRNA expression was examined by RT-PCR.NO production was estimated using NO kits.Results oxLDL significantly decreased iNOS mRNA expression and attenuated NO production.The inhibitory effect of oxLDL was associated with its concentration and degree of oxidative modification.When oxLDL was pretreated with α-lipoic acid,the iNOS mRNA expression and NO production were elevated as compared with oxLDL-treated group.Conclusions Oxidized but not native LDL decreases iNOS mRNA expression and NO production.The inhibitory effect is dose dependent and is associated with its degree of oxidative modification.α-lipoic acid can relieve the inhibitory effect of oxLDL on iNOS mRNA and NO production.