血管内膜平滑肌细胞增殖状态下的凋亡细胞标记

Evidence of apoptotic smooth muscle cells in intimal hyperlasia

目的探讨动脉损伤后内膜平滑肌细胞增殖状态下的凋亡细胞的水平及其出现的时间的部位，深入地研究血管成形术后再狭窄的形成机制，为抑制再狭窄的形成提供可能的干预措施。方法和结果应用球囊导管损伤小型猪髂动脉制备成内膜增殖所致的血管狭窄模型，采用计算机彩色图像分析系统动态观察损伤后１天、３天、６天、１２天和３０天的内膜平滑肌细胞增殖状况，并用末端转移酶介导的ｄＵＴＰ标记在ＤＮＡ３′－ＯＨ的方法（ＴＵＮＥＬ）来标记凋亡细胞。结果表明，损伤后６天以内，未出现凋亡细胞，从１２天起，仅在增殖的内膜中出现了较低水平的凋亡，即１２天（１．９４±０．４２）％和３０天（１．３６±０．３１）％，后二者差异无显著性。可以认为，较低水平的凋亡细胞可能是再狭窄形成过程中的病理学特征。结论平滑肌细胞的凋亡是血管损伤后狭窄形成过程中的一个重要的病理学特征，相比大量增殖的内膜平滑肌细胞，较低水平的凋亡可能是血管狭窄形成的机制之一，这提示，对低水平的凋亡进行适时适量的诱导，可能为抑制再狭窄提供新的选择。

Objective Previous studies indicated that despite the persistence of a relatively high level of injury induced proliferative activity, total arterial smooth muscle cells (SMCs) content did not change obviously after two weeks The aim of this study was to investigate the occurrence and extent of apoptosis in the course of restenotic formation Methods and Results The experimental models of vessel narrowness and intima thickness were established on minipigs′ iliac arteries by balloon injury, specimens were retrieved at timepoints of the 1st day, 3rd day, 6th day, 12th day and 30th day for dynamic observation Apoptotic SMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) The results were that apoptotic SMCs occurred only in the thickening intima 12 days after injury accompanied with the proliferative SMCs, the percentage of apoptosis was (1 94±0 42)% at 12th day and (1 36±0 31)% on 30th day respectively The low frequency of apoptosis compared with the proliferative SMCs was a feature in the restenotic pathology Conclusions Apoptosis participates in the pathogenetic process of intimal thickening and its level was low compared with proliferation The findings of the present study suggest that attempts to modulate apoptosis after vessel injury constitute a theoretical approach to the prevention of restenosis