Effect of arsenic trioxide on inhibition of restenosis after rabbit vascular injury and its mechanism  

氧化砷预防家兔血管损伤后再狭窄及其机理的研究(英文)

作　　者：赵智深[1] 黄从新[1] 王晶[1] 江洪[1] 李建军[1] 王晞[1] 

机构地区：[1]武汉大学人民医院心内科,武汉430060

出　　处：《Chinese Medical Journal》2002年第11期1608-1614,144-145,共7页中华医学杂志（英文版）

摘　　要：OBJECTIVE: To investigate the effect and mechanism of arsenic trioxide (As(2)O(3)) on the prevention of restenosis after vascular injury. METHODS: Apoptosis induction of As(2)O(3) on cultured rabbit vascular smooth muscle cells (VSMCs) in vitro was observed. Thirty-two New Zealand white rabbits were randomly divided into 2- and 4-wk study groups, and their controls. 10% As(2)O(3) at 2.5 mg x Kg(-1) x d(-1) or 0.9% sodium chloride was intraperitoneally infused for 3 days before left common carotid arteries were denudated with a balloon. After denudation 2- and 4-wk animals were sacrificed for morphometry and immunohistochemical studies on carotid arteries, and for histopathology on liver and kidney. RESULTS: It was shown via cellular morphology and DNA fragments in electrophoresis that promotion of As(2)O(3) on cultured vascular smooth muscle cell apoptosis was dependent upon its concentration and duration. Compared with the control animals, the mean vascular intimal proliferation areas were reduced in 2-wk study animals (P 0.05), while the mean vascular luminal areas were all enlarged in both study groups (all P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

关 键 词：Animals Apoptosis ARSENICALS DNA Female Flow Cytometry Male Muscle  Smooth  Vascular Oxides Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 RABBITS Vascular Diseases bcl-2-Associated X Protein 

分 类 号：R965[医药卫生—药理学]