氧化甾醇诱导血管平滑肌细胞凋亡及其作用特点的研究

The study of apoptosis and characterization of vascular smooth muscle cells (VSMCs) induced by oxysterols

目的研究３β，５α，６β－胆甾烷二醇（Ｔｒｉｏｌ）诱导血管平滑肌细胞（ＶＳＭＣｓ）凋亡及其与２５－羟胆固醇（２５－ＯＨ）比较的特点。方法体外培养ＶＳＭＣｓ、光镜、透射电镜及ＴＵＮＥＬ技术。结果ＶＳＭＣｓ经Ｔｒｉｏｌ处理后，贴壁层细胞呈现核染色质浓集，核碎裂和凋亡小体形成等凋亡的超微结构变化；ＴＵＮＥＬ显示ＶＳＭＣｓ凋亡细胞数随Ｔｒｉｏｌ浓度的增加而增多；剂量为 ３０ μｍｏｌ·Ｌ－１的 Ｔｒｉｏｌ和 ２５－ＯＨ诱导 ＶＳＭＣｓ的凋亡作用，前者不能而后者能被 ５０ μｍｏｌ·Ｌ－１的胆固醇所抑制。结论Ｔｒｉｏｌ能诱导ＶＳＭＣｓ凋亡，不同氧化甾醇可能有不同的作用通道和机制；氧化甾醇诱导ＶＳＭＣｓ凋亡可能是引起动脉粥样硬化斑块破溃，导致急性心血管事件发生的机制之一。

AIM To study the apoptosis and characterization of cultured vascular smooth muscle coils (VSMCs) induced by cholestan-3β, 5α, 6β-triol (Triol) and compared with 25-hydryoxycholestrol (25-OH). METHODS The culture of vascular mus- cle smooth cells (VSMCs), light and electron transmission microscopy and TdT-mediated dUPT nickend labeling (TUNEL) technique. RESULTS After being treated with oxyterols, VSMCs showed apoptosis of ultrastracture change including shrinkage, condensation of nuclear chromatin, fragmentation nuclei and formation of apoptotic body. TUNEL revealed that Triol-induced apoptosis in VSMCs was in a concentration-dependent manner. The effect of Triol and 25-OH at a 30 μmol· L-1 concentration in culture medium induced apoptosis of VSMCs, the former was not but the latter was inhibited by cholesterol at a 50 μmol·L-1 concentration. CONCLUSION Triol can induce VSMCs apoptosis in vitro and oxysterol-in- duced apoptosis in VSMCs may be mediated through various pathway and different mechanism. Oxysterol induced apoptosis in VSMCs may play an important role in triggering atherosclerosis plaque rupture and result to the onset of the acute coronary syndromes.