普罗布考抑制再狭窄与其调节功能性血管重构的关系

Probucol prevention against restenosis by regulating functional vascular remodeling after percutaneous transluminal angioplasty in rabbits

目的 研究普罗布考抗动脉成形术后再狭窄与其调节功能性血管重构的关系。方法 用 3 5F球囊导管构建兔动脉粥样硬化动脉成形术后再狭窄模型。动脉成形术 2wk后取其胸主动脉 ,固定染色并进行计算机图像分析 ;观察血管环对乙酰胆碱诱导的舒张百分率 ,然后再观察其对内源性收缩物质去甲肾上腺素 (NA)、KCl以及 5 羟色胺 (5 HT)的收缩反应性。同时 ,在动脉成形术 2wk后留其血清 ,观察普罗布考对动脉成形术后血清一氧化氮 (NO)含量的影响。结果 普罗布考明显增加血管管腔面积 ,减少新生内膜面积 ;可保护动脉成形术后血管的舒张功能 ,保护内皮细胞合成与释放内皮源性舒张因子NO ,降低血管对内源性收缩物质的收缩反应性。结论 普罗布考能提高扩张性血管重塑 ,抑制收缩性血管重塑 。

AIM To investigate the relationship between the prevention of probucol against restenosis and functional vascular remodeling after percutaneous transluminal angioplasty(PTA) in rabbits. METHODS New Zealand rabbit thoracic aorta atherosclerosis was induced by 3 5 F balloon catheter injury following a 4 week feeding of high cholesterol diet, and percutaneous transluminal angioplasty(PTA) was performed by using 3 5 F ballon catheter. Probucol(1 g·d -1 ) or vitamin E(400 mg·d -1 ) was administrated one week before PTA. Two weeks after PTA, lumen area,neointima area(NEA),medial area(MA) and NEA/MA were analyzed by computerimage system.The relaxation response of restenotic arteries to acetylcholine and the contractive response to norepinephrine, potassium chloride and serotonin of thoracic aorta rings were measured by bioassay. Nitric oxide of serum was measured by means of biochemical assay.RESULTS After two weeks of PTA, probucol increased lumen area and decreased neointima area significantly. The relaxation response of restenotic arteries to acetylcholine was significantly lower than that of normal arteries〔relaxation percent to acetylcholine (1 μmol·L -1 ):(18 4±4 0)% vs (63 5±6 4)%, P< 0 01〕, and the contractive response of restenotic vessel to norepinephrine, potassium chloride and serotonin was much more sensitivethan that of non restenotic vessel. However, probucol in hibited the relaxation response of rest enotic vessel to acetylcholine and decrease the contractive response to norepinephrine,potassium chloride and serotonin. Furtheremore,probucol could increase nitric oxide in serum. CONCLUSIONS Probucol preventes restenosis by enhancing constrictive vascular remodeling and inhibits expansive vascular remodeling after percutaneous transluminal angioplasty in rabbits.ctiveresponseto norepinephrine,potassiumchlorideandserotonin . Furtheremore,probucolcouldincreasenitricoxidein serum .CONCLUSIONS Probucol preventes restenosisbyenhancingconstrictivevascularremodel ingandinhibitsexpansivevascularremodelingafter percutaneoustransluminalangioplastyinrabbits. KEYWO