P27对大鼠胸主动脉球囊损伤后管腔狭窄的作用
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The Effect of P27 on Luminal Narrowing in Rats After Aortic Balloon Withdrawal Injury
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    目的探讨细胞周期素依赖性激酶抑制蛋白P27在大鼠胸主动脉球囊损伤后管腔狭窄过程中的表达变化规律及全反式维甲酸对其的影响。方法将54只400~500g的雄性SD大鼠随机分为三组,全反式维甲酸治疗组大鼠行胸主动脉球囊损伤术,术前4天开始予全反式维甲酸(30mgkg.d)灌胃至术后处死;单纯手术组大鼠行胸主动脉球囊损伤术;对照组不行球囊损伤,作为正常对照;手术组和对照组予对照用芝麻油灌胃。分别于术后2、7、14、28天取胸主动脉用HE染色、免疫组织化学和计算机图像分析仪进行形态学、增殖细胞核抗原和P27表达水平检测。结果①正常动脉壁不表达增殖细胞核抗原,球囊损伤后开始表达,术后2天中膜表达显著(24.08±2.35);术后7天新生内膜高度表达增殖细胞核抗原(35.32±3.46),而中膜表达明显下降(9.47±1.56);后内膜、中膜增殖细胞核抗原表达均逐渐下降,28天时形成显著的新生内膜(0.173±0.030mm2),管腔狭窄(1.641±0.088mm2)。②正常动脉壁显著表达P27(19.29±1.54),损伤后中膜表达迅速下降,2天时达最低水平(2.93±0.55),后逐渐回升;14天、28天时新生内膜中可见P27表达,并逐渐增多(14天:10.30±1.39;28天:16.01±1.33)。③P27表达与增殖细胞核抗原表达呈显著负相关(r=-0.868,p<0.001)。④全反式维甲酸治疗后明显抑制中膜P27的下调(2天:7.67±1.27),促进新生内膜中P27表达(7天:6.09±1.04;14天:22.60±2.46;28天:26.23±2.43),同时显著抑制增殖细胞核抗原的表达(2天时中膜:12.11±1.84;7天时内膜:16.83±1.02),新生内膜面积明显减少(0.075±0.017mm2),管腔面积(1.901±0.085mm2)明显大于单纯手术组(P均<0.01)。结论P27低表达在动脉损伤后管腔狭窄过程中具有重要意义。

    Abstract:

    Aim To investigate the influence of all-trans retinoic acid (ATRA) on the process of luminal narrowing, the expression of some cell cycle modulatory factors in rats artery after aortic balloon withdrawal injury. Methods 54 SD rats were randomly divided into 3 groups. In control group (n=6) rats were killed at the 28th day after procedure. In operation group (n=24) and ATRA group (n=24) rats had balloon induced endothelium denudation at thoracic aorta and were killed at the 2nd, 7th, 14th, 28th day after artery injury. All rats were predosed with ATRA (30 mg/kg.d) or corn oil by gavage 4 days before injury and continued to each indicated time. After the thoracic aorta were harvested, we used immunohistochemistry staining to measure the protein expression of cyclin dependent kinase inhibitor P27 and proliferation cell nuclear antigen. Meanwhile vessel morphological measurement was taken. Results ①In normal rat arteries P27 was detected. After balloon injury, P27 expression in media decreased, reached the lowest level at the 2nd day and then upregulated while vascular smooth muscle cell (VSMC) reached peak proliferation at the 2nd day and then decreased quickly. In neointima, VSMC proliferated extremely at the 7th day, P27 could be detected at the 14th and 28th day when the proliferation of VSMC decreased. ②In ATRA-treated group P27 downregulation was inhibited in media, and P27 was already present in the neointima at the 7th day and strongly expressed at the 14 th and 28 th day while the proliferation of VSMC was significantly decreased (p<0.01). As a result ATRA group had a smaller noeintima /media area ratio, larger internal or external elastic lamina area and luminal area (p<0.01). ③The expression of P27 and the cell proliferation were in remarkable negative correlation (p<0.001). Conclusion The decreased expression of P27 may have an important role in the process of luminal narrowing after aortic balloon withdrawal injury.

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褚现明,李冰,杜日映,钟志欢,崔国方,董果雄,张先明,张斌,李宁. P27对大鼠胸主动脉球囊损伤后管腔狭窄的作用[J].中国动脉硬化杂志,2006,14(5):417~421.

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  • 收稿日期:2005-07-11
  • 最后修改日期:2006-04-29
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