紫杉醇对兔血管内皮和平滑肌细胞增殖影响的时间效应关系
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国家自然科学基金(30270568,30400517)资助


Effect of Paclitaxel on the Time Course of Rabbit Vascular Smooth Muscle Cells and Endothelial Cells Growth
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    摘要:

    目的 观察紫杉醇对兔血管内皮和平滑肌细胞增殖影响的时间效应关系,探讨药物洗脱支架植入后,损伤血管修复过程中延迟再狭窄发生的部分细胞学机制。方法 将兔平滑肌接种于上室、内皮细胞接种于下室建立细胞共培养体系,根据下室中内皮细胞生长状态随机分为融合内皮组、对数内皮组、平滑肌对照组和内皮对照组,于融合内皮组和对数内皮组下室加入10nmol/L紫杉醇干预2 0min ,分别于干预前、干预后第1天、第3天、第7天和第10天检测平滑肌细胞和内皮细胞氚标胸腺嘧啶脱氧核苷掺入率,并作细胞计数。结果 紫杉醇干预后第1天和第3天,对数内皮组和融合内皮组平滑肌细胞氚标胸腺嘧啶脱氧核苷掺入率和细胞计数均明显低于平滑肌对照组(对数内皮组和融合内皮组平滑肌细胞氚标胸腺嘧啶脱氧核苷掺入率分别为第1天5 4 %±4 %和5 6 %±5 % ,第3天6 5 %±3%和6 3%±3% ;细胞计数分别为第1天6 4 %±6 %和6 2 %±4 % ;第3天6 8%±5 %和6 6 %±5 % ,P<0 .0 5 )。对数内皮组内皮细胞氚标胸腺嘧啶脱氧核苷掺入率和细胞计数明显低于内皮对照组(对数内皮组内皮细胞氚标胸腺嘧啶脱氧核苷掺入为第1天75 %±9% ,第3天81%±6 % ;细胞计数为第1天72 %±7% ,第3天80 %±7% ;P<0 .0 5 ) ;紫杉醇干预后第7天和第10天,融合内皮组平滑肌细胞氚标胸腺嘧啶脱氧核苷掺入率和细胞计数仍明显低于对照组平滑肌细胞(融合内皮组平滑肌细胞氚标胸腺嘧啶脱氧核苷掺入率为第7天6 9%±5 % ,第10天73%±4 % ;细胞计数为第7天72 %±5 % ,第10天76 %±6 % ;P<0 .0 5 ) ,对数内皮组内皮细胞氚标胸腺嘧啶脱氧核苷掺入率和细胞计数与内皮对照组相比均无显著差异,对数内皮组平滑肌细胞氚标胸腺嘧啶脱氧核苷掺入率和细胞计数在紫杉醇干预后第7天与平滑肌对照组相比也无统计学差异,干预后第10天时明显高于平滑肌对照组(氚标胸腺嘧啶脱氧核苷掺入率为10 7%±5 % ,细胞计数为112 %±7% ,P<0 .0 5 )。结论 紫杉醇短时作用2 0min即能持续抑制血管内皮和平滑肌细胞增殖,紫杉醇干预后平滑肌细胞延迟增殖与内皮细胞延迟再生密切相关

    Abstract:

    Aim To investigate the effect of paclitaxel on the time course of rabbit vascular smooth muscle cells (SMC) and endothelial cells (EC) growth. Methods In the cell coculture system, rabbit EC were seeded in the lower chamber and SMCs in the upper chamber. Four groups were divided: confluent EC group,proliferative EC group, EC control group and SMC control group. Paclitaxel of 10 nmol/L was added to the lower chamber of the confluent and proliferative EC group and act for 20 minutes. 3 H-TdR incorporation and cell counting were assayed respectively after 0, 1, 3, 7 and 10 d to determine the effect of paclitaxel on the time course of vascular EC and SMC growth. Results At 1 and 3 d after paclitaxel was added, the 3H-TdR incorporation and cell counting of SMC in the confluent and proliferative EC group were both significantly lower than those in the SMC control group (confluent EC group, proliferative EC group, 3 H-TdR incorporation was respectively: 1d:54%±4%, 56%±5%; 3 d: 65%±3%, 63%±3%; cell counting was respectively: 1 d: 64%±6%, 62%±4%; 3 d: 68%±5%, 66%±5%; n=6, p<0.05). The 3 H-TdR incorporation and cell counting of EC in the proliferative EC group were also significantly lower than those in the EC control group ( 3 H-TdR incorporation: 1 d: 75%±9%, 3 d: 81%±6%; cell counting: 1 d: 72%±7%, 3 d: 80%±7%; n=6, p<0.05). At 7 and 10d after paclitaxel was added, the 3 H-TdR incorporation and cell counting of SMC in the confluent EC group were still lower than those in the SMC control group ( 3 H-TdR incorporation: 7 d: 69%±5%, 10 d: 73%±4%; cell counting: 7 d: 72%±5%, 10 d: 76%±6%; n=6, p<0.05). However, the 3 H-TdR incorporation and cell counting of EC in the proliferative EC group have no statistical significance compared with the EC control group( 3 H-TdR in-corporation: corporation: 7 d: 97%±5%, 10 d: 101%±4%; cell counting: 7 d: 95%±4%, 10 d:

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武晓静,黄岚,周骐,宋明宝,于世勇,晋军.紫杉醇对兔血管内皮和平滑肌细胞增殖影响的时间效应关系[J].中国动脉硬化杂志,2005,13(1):5~8.

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  • 收稿日期:2004-04-08
  • 最后修改日期:2004-12-02
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