中国血液净化

›› 2008, Vol. 7 ›› Issue (2): 81-84.

• 基础研究 • 上一篇    下一篇

他汀类药物对高磷介导血管平滑肌细胞成骨细胞转分化 和钙化的影响

郑曼韬 薛 骏 游怀舟 包福祥 周士铿   

  1. 上海市南汇区中心医院
  • 收稿日期:2007-11-16 修回日期:1900-01-01 出版日期:2008-02-12 发布日期:2008-02-12

Statins protect human aortic smooth muscle cells from osteoblast transdifferentiation and calcification induced by high concentration phosphate

ZHENG Mantao, 2XUE Jun, 2YOU Huaizhou, 1BAO Fuxiang, 1ZHOU Shikeng   

  • Received:2007-11-16 Revised:1900-01-01 Online:2008-02-12 Published:2008-02-12

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摘要： 【摘要】目的 探讨他汀类药物对高磷介导血管平滑肌细胞成骨细胞转分化和钙化的影响。方法 将体外培养的人主动脉平滑肌细胞(HASMC)分成对照组(常规Medium 231培养基)、正常磷浓度组(Pi1.5mmol/L)和高磷组(Pi2.5mmmol/L)。Real-time PCR测定干预72h后细胞的核结合因子α(cbfα)和骨桥蛋白(OPN)水平，测定干预14d后上清液的钙浓度。HASMC在浓度为0.1umol/L的阿托伐他汀和2.5mmol/L的Pi培养基中共同孵育14d后，检测HASMC的钙含量。结果 培养72h后，cbf-α在Pi 2.5mmol/L组的mRNA表达明显高于对照组(50.02±0.38 vs. 1.02±0.35，P＜0.001)，而Pi 1.5mmol/L组与对照组无明显差别(1.07±0.15 vs. 1.02±0.35, P＞0.05)。Pi 2.5mmol/L组的OPN表达亦明显高于对照组(14.62±0.35 vs. 1.05±0.16)，而Pi 1.5mmol/L组与对照组无明显差别(0.99±0.10 vs. 1.05±0.16)。高磷组钙含量明显高于对照组(115±2.43 vs. 4.08±0.32, P＜0.001)，而Pi 1.5mmol/L组与对照组相比无明显变化(5.01±0.21 vs. 4.08±0.32，P＞0.05)。阿托伐他汀能使高磷诱导HASMC的钙沉积明显减少(115±2.43 vs. 58±2.65 ug/mg蛋白，P＜0.01)。结论 高磷作用能明显增加HASMC的cbfα-1的表达，明显增加HASMC成骨细胞标志性蛋白OPN的表达，使HASMC向成骨细胞转分化，进而促进HASMC钙化；阿托伐他汀能抑制高磷诱导的HASMC的钙化作用。

关键词: 高磷, 阿托伐他汀, 人主动脉平滑肌细胞, 成骨细胞, 转分化, 钙化

Abstract:
【Abstract】 Objective To investigate the role of statins on high concentration phosphate-induced osteoblast transdifferentiation and calcification of vascular smooth muscle cells. Method Human aortic smooth cells (HASMC) were cultured in normal control medium, normal phosphate medium (1.5mmol/L phosphate) and high phosphate medium (2.5mmol/L phosphate), respectively. The expression of core binding factor-α1 (cbf-α1) and osteopontin (OPN) was measured by real-time quantitative PCR after culture in the medium for 72 hours, and calcium concentration in the medium was also measured after the culture for 14 days. HASMC were then cultured in high phosphate medium containing 0.1 umol/L atorvastatin for 14 days, and calcium content in HASMC was determined. Results Real-time quantitative PCR showed that the expression of cbf-α1 was significantly higher in high phosphate group than in control group (50.02±0.38 vs. 1.02±0.35, P＜0.001), but without difference between normal phosphate group and control group (1.07±0.15 vs. 1.02±0.35, P＞0.05). The expression of OPN was also remarkably higher in high phosphate group than in control group (14.62±0.35 vs. 1.05±0.16). The calcium content in HASMC was significantly higher in high phosphate group than in control group (115±2.43 vs. 4.08±0.32, P＜0.001), but was similar in normal phosphate group and control group (5.01±0.21 vs. 4.08±0.32，P＞0.05). Atorvastatin significantly decreased the phosphate-induced calcium deposit (115±2.43 vs. 58±2.65 ug/mg protein, P＜0.01). Conclusion High phosphate induced osteoblast transdifferentiation and calcification of HASMC. The high phosphate induced calcification of HASMC could be inhibited by atorvastatin.

Key words: Atorvastatin, Human aortic smooth muscle cells, Osteoblastic transdifferentiation, Calcification