大鼠胸主动脉球囊损伤后平滑肌细胞PCNA和P27表达的变化

目的探讨大鼠胸主动脉球囊损伤后增殖细胞核抗原(PCNA)、细胞周期蛋白依赖性激酶抑制蛋白P27表达变化规律。方法30只400～500g的雄性SD大鼠随机分为2组。手术组(n=24)行球囊损伤大鼠胸主动脉术;对照组(n=6)不行球囊损伤,作为正常对照。于术后2d、7d、14d、28d取胸主动脉应用HE染色、免疫组化和计算机图像分析法进行形态学、PCNA和P27表达水平检测。结果(1)正常动脉壁不表达PCNA,球囊损伤后开始表达,术后2d时中膜表达显著(24.08±2.35);术后7d出现新生内膜,PCNA在内膜高度表达(35.32±3.46)而中膜表达已明显下降(9.47±1.56);后内膜、中膜表达均逐渐下降,28d时形成显著的新生内膜(0.173±0.030)mm2,管腔狭窄;(2)正常动脉壁显著表达P27(19.29±1.54),球囊损伤后中膜表达迅速下降,2d达最低水平(2.93±0.55),后逐渐回升;14d、28d新生内膜中可见P27表达,并逐渐增多;(3)P27表达与PCNA表达呈显著负相关(r=0.868P<0.001)。结论球囊损伤大鼠主动脉后管壁P27表达下调伴随PCNA表达上调,血管平滑肌细胞恢复增殖能力并向内膜下迁移并过度增殖,从而形成显著的新生内膜、管腔狭窄。

The Change of the Expression of the Proliferation Cell Nuclear Antigen and p27 in Rats after Aortic Balloon Withdrawal Injury

Objective To investigate the the process of luminal narrowing, the expression of some cell cycle modulatory factors in rats artery after aortic balloon withdrawal injury. Methods Thirty SD rats were randomly divided into 2 groups.Group 1 (n=6)served as controls and were killed 28 days after procedure.Group 2 (n=24) had balloon induced endothelium denudation at thoracic aorta and were killed at 2,7,14,28 days after artery injury .After the thoracic aorta were harvested, we used immunohistochemistry to measure the expression Level of cyclin dependent kinase inhibitor p27kip1 and proliferation cell nuclear antigen (PCNA). Meanwhile vessel morphological measurement was taken. Results (1)In normal rat arteries p27 was detected. balloon injury,p27 expression in media decreased ,reached the lowest level at day 2 and then upregulated while vascular smooth muscle cell(VSMC) reached peak proliferation at day 2 and then decreased quickly. In neointima , VSMC proliferated extremely at day 7,p27 could be detected at day 14 and 28 when the proliferation of VSMC decreased . As a result at 28d after balloon injury a outstanding noeintima formed, smaller internal or external elastic lamina area and luminal area formed(P<(0.01)); (2)The expression of p27 and the cell proliferation were in remarkable negative correlation(P<(0.001)).Conclusion The downregulation of p27 while upregulation of PCNA has a important role in the proliferation of VSMC,neointima formation and the luminal narrowing.