阿魏酸钠拮抗氧化型脂蛋白(a)对人动脉平滑肌细胞的作用

Sodium Ferulate protects human aortic smooth muscle cells against oxidized Lipoprotein(a)

目的 :研究脂蛋白 (a) [Lp(a) ]氧化前后致人动脉平滑肌细胞 (SMC)增殖及细胞内游离钙浓度([Ca2 + ] i)的变化 ,观察阿魏酸钠 (SF)对其的影响。方法 :Lp(a)经体外Cu2 + 氧化法氧化 ,硫代巴比妥酸 (TBARS)比色法检测氧化程度 ,培养的人动脉SMC中分别加入不同浓度SF ,作用 1 2h后再与天然和氧化型Lp(a)共同孵育 ,以MTT比色法、流式细胞仪检测细胞增殖状况 ,采用荧光探针Fura - 2 /AM检测细胞 [Ca2 + ] i。结果 :氧化型Lp(a)促人动脉SMC增殖的同时亦明显增加了 [Ca2 + ] i 水平 ,作用较天然Lp(a)明显 ,SF(40 ,80mg/L)可显著抑制氧化型Lp(a)所致的细胞增殖和 [Ca2 + ] i增加 ,并呈剂量效应关系 ,而对天然Lp(a)所致的细胞增殖和 [Ca2 + ] i 增加无明显影响。结论 :氧化型Lp(a)通过升高 [Ca2 + ] i 而显著促动脉SMC增殖可能是其致动脉粥样硬化的机制之一 。

AIM: To investigate the influences of native and oxidized lipoprotein(a) on human arterial smooth muscle cell (SMC) proliferation, change of intracellular free calcium concentration ([Ca 2+ ] i) and the protective effect of sodium ferulate(SF). METHODS: Lp(a) was oxidized by Cu 2+ and the extent of oxidation was assessed by the MDA content.Human SMC were incubated in culture media with SF for 12 h, then exposed to Lp(a) and oxidized-Lp(a), respectively. MTT colorimetry and flow cytometry were used to evaluated the proliferation of SMC and flurorescent indicator Fura-2/AM was used to determined [Ca 2+ ] i. RESULTS: ox-Lp(a) significantly promoted proliferation of SMC and increased[Ca 2+ ] i compared with Lp(a). SF(40,80 mg/L) remarkedly inhibited SMC proliferation and decreased the rising of [Ca 2+ ] i induced by ox-Lp(a) in a dose-dependent manner, but no effect on SMC proliferation and the increase in [Ca 2+ ] i induced by Lp(a).CONCLUSION: ox-Lp(a) induces the strong growth-promoting effect in SMC through increasing in [Ca 2+ ] i, which might be one of the cellular mechanisms responsible for the higher atherogenic potential of ox-Lp(a) compared with Lp(a), and this process can be prevented by inhibiting of oxidation by SF.