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目的 探讨应用三氧化二砷 (As2 O3)预防血管损伤后再狭窄的效果及其作用机理。方法 观察As2 O3对培养兔血管平滑肌细胞 (VSMCs)凋亡的影响。 32只新西兰白兔随机分为 2、4周实验组和对照组 ,分别 10 %As2 O32 5mg·Kg 1·d 1或等量生理盐水腹腔注射 3天 ,应用球囊损伤左颈总动脉。处死动物取血管作形态学和免疫组化检测 ,并检查肝脏、肾脏组织学变化。结果 细胞形态学和DNA电泳梯形带证实 ,As2 O3诱导培养VSMCs凋亡 ,与药物浓度和作用时间呈依赖性。与对照组相比 ,2 wk实验组血管内膜增殖面积显著减少 (P <0 0 5 ) ,4 wk组内膜面积无明显差异 ;但 2 ,4 wk组的管腔面积均有明显增大 (P均 <0 0 5 )。与对照组相比 ,实验组 2 ,4 wk免疫组化显示bcl 2表达下调 (P均 <0 0 5 ) ,Bax表达上调 (P分别 <0 0 1,0 0 5 ) ,均与相对应的血管内膜增生受抑制 ,血管腔面积扩大相吻合结论 As2 O3诱导VSMCs凋亡和有效预防实验性血管损伤后再狭窄 ,均与下调bcl 2和上调bax表达有关
Objective To investigate the effect of arsenic trioxide (As 2 O 3) on restenosis after vascular injury and its mechanism. Methods The effect of As2 O3 on the apoptosis of cultured rabbit vascular smooth muscle cells (VSMCs) was observed. Thirty-two New Zealand white rabbits were randomly divided into experimental group and control group at 2 and 4 weeks. The animals were infused with 10% As2 O32 5 mg · Kg 1 · d 1 or an equal volume of normal saline for 3 days respectively. Animals were sacrificed for morphological and immunohistochemical examination of the blood vessels, and liver and kidney histological changes were examined. Results Cell morphology and DNA ladder electrophoresis confirmed that VSMCs apoptosis induced by As2 O3 was dependent on drug concentration and time. Compared with the control group, the area of intimal proliferation was significantly decreased in the 2-week experimental group (P <0.05), while there was no significant difference in the intima area in the 4-week group. However, the luminal area in the 2 and 4-week groups was significantly increased (All P <0 05). Compared with the control group, the expression of bcl-2 was down-regulated at 2 and 4 weeks in the experimental group (all P <0.05) and the expression of Bax was up-regulated (P <0 0 and 10 0 5, respectively) Intimal hyperplasia was inhibited and vascular lumen was enlarged. Conclusions Arsenic trioxide (As 2 O 3) induced apoptosis of VSMCs and prevention of restenosis after experimental vascular injury were associated with down-regulation of bcl 2 and up-regulation of bax expression