摘要
目的观察缺氧对培养的兔胸主动脉平滑肌细胞增殖的影响,以卡托普利为对照探讨普鲁托品平滑肌细胞增殖的作用.方法采用析因实验设计,研究普鲁托品和卡托普利在常氧或缺氧条件下对培养兔平滑肌细胞数量、[3H]-TDR、MTT的作用.结果缺氧明显增加平滑肌细胞的数量,促进DNA的合成及细胞超微结构改变;1μmol/L、10μmol/L、100μmol/L普鲁托品均能逆转缺氧所致的细胞数量、MTT、[3H]-TDR的变化,且随浓度的增加,此抑制作用愈显著.结论缺氧本身可诱导平滑肌细胞增殖,普鲁托品抑制缺氧诱导的平滑肌细胞增殖,可望成为临床抗动脉粥样硬化或PTCA后再狭窄新的有效药物.
Abstract
Objective To examine the effect of hypoxia on proliferation expression in cultured rabbit aortic vascular smooth muscle cells(VSMC) and determine whether cell proliferation are altered under protopine conditions compared with captopril conditions. Methods Smooth muscle cells isolated from rabbit thoracic aorta were cultured and used in the 3～5 passages. Quiescent cultures of VSMC with 0,10-6 , 10-5,10-4 mol/L protopine or 10～6 mol/L captopril were exposed to hypoxia(3 %O2+5 %CO2 +92%N2) or normoxia(5%CO2+95% air) in 5% serum medium respectively,and the number of VSMC, [3 H]-TDR incorporation, MTT, intracellular calcium concentration and microstructure of VSMC were performed for the effects of proliferation of cultured rabbit VSMC after 24 hours. Results Cells exposed to hypoxia for 24 hours exhibited a significant increase in [3 H] thymidine incorporation comparing normoxic controls. In addition,10-6,10-5,10-4 mol/L of protopine or 10-6 mol/L of captopril significantly decreased the number of VSMC,the absorbance (A) of MTT and [3 H]-TDR incorporation induced by hypoxia( P ＜0.05, or P ＜0.01), further, the two drugs have cooperation effects,especially in hypoxia group. Conclusion Protopine have an effective inhibition on proliferation of cultured VSMC induced by hypoxia. Furthermore,the inhibition of protopine to the proliferation of VSMC is more significantly induced by hypoxia than treated by normoxia. This suggested that protopine could prevent development of atherosclerosis associated with arterial wall hypoxia.
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