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中国临床药理学与治疗学 ›› 2002, Vol. 7 ›› Issue (1): 9-13.

• 基础研究 • 上一篇    下一篇

氧化甾醇抑制血管平滑肌细胞(VSMC)增殖及诱导其凋亡的作用1

洪华山, 林岚, 王一波, 江琼, 郑关毅, 陈良龙, 陈建华   

  1. 福建医科大学附属协和医院心内科, 福建省冠心病研究所, 福州 350001
  • 收稿日期:2001-10-29 修回日期:2002-01-08 出版日期:2002-02-26 发布日期:2020-11-27
  • 通讯作者: 洪华山, 男, 37 岁, 博士, 副教授, 硕士导师, 享受国务院政府特殊津贴。研究方向:动脉粥样硬化和慢性心肌缺血基础和临床研究。Tel:0591-3357896-8475/8455 E-mail:honghuashan@hotmail.com
  • 基金资助:
    1 福建省教育厅(K 99057) 基金资助课题

Inhibitive proliferation and promotive apoptosis effects of oxysterols on vascular smooth muscle cells (VSMC)

HONG Hua-Shan, LIN Lan, WANG Yi-Bo, ZHENG Guan-Yi, CHEN Liang-Long, CHEN Jian-Hua   

  1. Department of Cardiology, Union Hospital of Fujian Medical University, Fujian Institute of Coronary Heart Disease,Fuzhou 350001
  • Received:2001-10-29 Revised:2002-01-08 Online:2002-02-26 Published:2020-11-27

摘要: 目的: 研究 3β, 5α, 6β-胆甾烷三醇(Triol) 和25-羟胆固醇(25OH) 对 VSMC 增殖的影响, 探讨氧化甾醇在动脉粥样硬化(AS) 发病中的作用和意义。 方法: 培养和鉴定新西兰白兔主动脉 VSMC; 以含不同浓度的Triol 和 25OH 的培养液作用于VSMC 为实验组, 不含氧化甾醇或含胆固醇的培养液作为对照组。 VSMC 增殖及其代谢活性以 WST-1 测定, 细胞凋亡以光镜、透射电镜、脱氧核苷酸末端转移酶介导脱氧尿苷三磷酸缺口末端标记(TUNEL) 判断。结果: 在1×10-9 ~ 1 ×10-7mol·L-1 范围的 Triol 和 25OH 对VSMC 的 WST-1代谢活性无明显变化(P >0.05), 而≥1×10-6mol·L-1 的氧化甾醇则使其代谢活性显著下降 (P <0.01); ≥20 ×10-6 mol·L-1 的 Triol 和25OH 诱导VSMC 胞体皱缩变小、染色质在核周边浓集、核碎裂、 空泡和凋亡小体形成等超微结构变化; TUNEL 呈阳性反应。结论: 小剂量氧化甾醇无促进VSMC 增殖而较大剂量氧化甾醇可诱导 VSMC 凋亡。

关键词: 氧化甾醇, 血管平滑肌细胞, 增殖, 凋亡动脉粥样硬化

Abstract: AIM: To study the effects of cholestan-3β, 5α, 6β-triol (Triol ) and 25-hydroxycholesterol (25OH) on proliferation, apoptosis of vascular smooth muscle cells(VSMC) and to explore the effects and signifi-cance of oxysterols in atherogenesis.METHODS: VSMC of aorta of New Zealand white rabbit were cultured and i-dentified.VSMC incubated with or without Triol and 25OH or cholesterol, at different concentrations, was as experimental groups or control group.Cell proliferation was measured with WST-1.Cell apoptosis was evaluated by light and electron transmissionmicroscopy and terminal deoxynuocleotidyl transferase (TdT)-mediated dUPT nick-end labeling (TUNEL). RESULTS: The metabolic ac-tivity of VSMC wasnot different between at low dose (1× 10-9 -1 ×10-7 mol·L-1 ) of Triol and 25OH experi-mental groups and control group (P >0.05), but it de-creased significantly at higher dose (≥ 1 × 10-6 mol·L-1 ) of oxysterols groups (P <0.01). After being treated with higher dose(≥20×10-6 mol·L-1 ) of oxyterols, VSMC showed apoptosis of ultrastracture change including shrinkage, condensation of nuclear chro-matin, fragmentation nuclei and formation of apoptotic body.TUNEL revealed that Triol-induced apoptosis in VSMC was in a concentration-dependent manner.CONCLUSIONS: Triol and 25OH, at low dose, have not growth effect on VSMC, but at higher dose can induce VSMC apoptosis.Oxysterol-induced VSMC apoptosis may trigger plaque rupture and play an important role in atherogenesis.

Key words: oxysterol, vascular smooth muscle cell, proliferation, apoptosis, atherosclerosis

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