全反式维甲酸对兔颈动脉粥样硬化病灶VSMC增殖信号传导途径的影响

Effects of All-trans Retinoic Acid(ATRA)on the Proliferation Signal Conduction Pathway of VSMC in Atherosclerotic Focus of Infection in Rabbits Carotid Artery

目的探讨全反式维甲酸(ATRA)对兔颈动脉粥样硬化病灶中血管平滑肌细胞(VSMC)转型、迁移和增殖信号传导机制的影响。方法新西兰雄性大白兔随机分为正常对照组(n=12),手术组(n=12),及ATRA治疗组(n=12)。三组均高脂饮食两周后,手术组用空气干燥法制作颈动脉内膜损伤模型。ARTA治疗组于术前3 d开始给予全反式维甲酸灌胃,直至处死,其余操作同手术组。术后分别于14,28 d随机处死。采取颈动脉标本,对血管粥样硬化病变进行大体形态学观察,用免疫组化方法检测血管粥样硬化病灶中MAPK、C-fos的表达水平。结果通过形态学观察治疗组的内膜增生程度明显低于手术组(P＜0．05),治疗组增生内膜中MAPK、C-fos表达水平较手术组明显减轻(P＜0．05)。结论ARTA能抑制兔颈动脉内膜损伤后新生内膜过度增殖,其机制可能为通过抑制丝裂原活化蛋白激酶(Mitogen Activated Protein Kinase,MAPK)及原癌基因C-fos的表达。

Objective To investigate the influence of all-trans retinoic acid （ATRA） on the mechanisms of transconformation, immigration and multiplication signal conduction of vascular smooth muscle cell in carotid atherosclerosis in rabbits. Methods Rabbits were randomly divided into three groups： normal group（n =12）, control group（n =12） and ATRA treated group（n =12）. All the three groups were fed by high-cholesterol diet and control group was made into carotid atherosclerosis model using air-drying after two weeks. The ATRA treated group was fed by all-trans retinoic acid. On the 14d and 28d, the target vessel was taken out, MAPK and C-fos were observed by immunostaining. The carotid arteries were harvested several weeks after the operation. Results proliferation degree and expression level of MAPK and C-fos in endomembrane of treated group is respectively lower （ P 〈 0.05 ） and higher （ P 〈 0. 05 ） than operated group, which is observed morphologically. Conclusion Our results indicate that ATRA treatment can inhibit atherosclerotic progression by inhibiting the proliferation of vascular smooth muscle cells. The mechanism may be related to inhibition of the expression of MAPK and C-fos in vascular smooth muscle cells.