全反式维甲酸对球囊剥脱大鼠胸主动脉内皮后平滑肌细胞增殖和P21表达的影响

The influnce of all-trans retinoic acid on the proliferation of VSMC and the expression of p21 in rats after aortic balloon withdrawal injury.

目的:探讨全反式维甲酸(ATRA)对球囊损伤大鼠胸主动脉后管腔狭窄、血管平滑肌细胞(VSMC)增殖及细胞周期依赖性激酶抑制蛋白P21表达规律的影响。方法:54只SD大鼠随机分为三组,对照组不进行球囊损伤,术后28天处死;手术组和ATRA治疗组行球囊剥脱胸主动脉内皮术,分别于术后2d、7d、14d、28d处死。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P21表达水平检测。结果:①正常动脉壁不表达PCNA及P21。②手术组中膜VSMC术后2d PCNA表达达高峰,后迅速下降;而新生内膜在术后7d出现并高表达PCNA,14d、28d内膜迅速增厚,其中PCNA表达逐渐下降。P21在术后14d新生内膜中可见少量表达,28d表达增多。③ATRA治疗组术后7d新生内膜中已有P21表达,14d、28d大量表达,而PCNA的表达明显低于手术组,显著抑制VSMC的迁移和增殖、内膜增生和管腔狭窄(P<0.01)。④P21表达与PCNA表达呈负相关(P<0.001)。结论:ATRA可通过诱导P21蛋白表达,抑制VSMC迁移和增殖,从而抑制球囊剥脱大鼠胸主动脉内皮后新生内膜过度增生和管腔狭窄。

Objective： To investigate the influnce of all-trans retinoic acid （ATRA） on the process of neointimal formation,vascular remodeling, the expression of some cell cycle modulatory factors in rals after aortic balloon withdrawal injury. Methods：54 SD rats were randomly divided into 3 groups：Control operation group did not have ballon injury and were killed 28 days after procedure; Operation group and ATRA group had balloon induced endothelium denudation at thoracic aorta and were killed at 2,7, 14,28 days after artery injury. All rats were predosed with ATRA （30mg·kg^-1·d^-1） or corn oil by gavage 4 days before injury and conlinued Io each indicated time. After the thoracic aorta were harvested, we used immunohistochemistry staining to measure the protein expression of cyclin dependent kinase inhibitor p21cipl and proliferation cell nuclear antigen PCNA. Meanwhile vessel morphological measurement was taken. Result （1） In normal rat arteries p21 was not detected, After balloon injury, vascular smooth muscle cell （VSMC） proliferation reached peak proliferation at day 2 and decreased quickly in media. In tunica intima, VSMC proliferated extremely at day 7, p21 can be detected at day 14 and 28 when VSMC proliferation decreased. （2） in ATRA-treated group p21 was already present in the neointima at day 7 and strongly expressed at day decreased significantly. The expression of p21 and the correlation.As a result ATRA group had a outstanding luminal area. Conclusion：Inhibiting VSMC proliferation mechanism by which ATRA reduced neointima formation 14 and 28 while the VSMC proliferation was cell proliferation are in remarkable negative smaller noeintima/media area ratio and larger by induced expression of p21 may be one and elicited favorable geometric remodeling of the injuried rat aortic artery.