全反式维甲酸对兔颈动脉粥样硬化病变中Cdk2表达及血管平滑肌细胞增生的影响

Influence of All-trans Retinoic Acid on the Expression of Cdk2 and Proliferation of Vascular Smooth Muscle Cells in Carotid Atherosclerosis in Rabbits.

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内膜的增生、血管平滑肌细胞(VSMCs)增殖、增殖细胞核抗原(PCNA)及细胞周期素依赖性激酶Cdk2表达规律的影响。方法36只新西兰雄性大白兔随机分为3组:正常饮食组、手术组、ARTA治疗组,每组12只。手术组和治疗组均给予高脂饮食,两周后用空气干燥法制作颈动脉内膜损伤模型,治疗组于术前3d开始给予ATRA灌胃。于术后1、4周处死动物,取病变血管应用HE染色、免疫组化和计算机图像分析法进行形态学、PCNA和Cdk2表达水平的检测。结果①正常动脉壁未见PCNA及Cdk2表达。②手术组在术后第1周时内膜开始增生,第4周增生明显,且出现泡沫细胞、脂质核心形成、管腔狭窄;增生内膜中Cdk2表达水平增高。③治疗组Cdk2的表达明显低于手术组(P<0.05),VSMCs的迁移、增殖、内膜增生和管腔狭窄显著减轻(P<0.05)。④PCNA表达与Cdk2表达呈显著正相关(P<0.01)。结论ARTA可通过抑制Cdk2表达,抑制VSMCs的迁移和增殖,从而抑制兔颈动脉粥样硬化新生内膜过度增生和管腔狭窄。

Objective To investigate the influence of all-trans retinoic acid （ATRA） on the neoinfimal formation, vasclar remodeling, the expression of Cdk2 in carotid atherosclerosis in rabbits. Methods Thirty-six New Zealand rabbits were randomly divided into 3 groups： normal group （n = 12）, control group （n= 12） and ATRA- treated group （n= 12）. The control group and ATRA-treated group were fed with high - cholesterol diet and two week＇ s later they were induced into carotid atherosclerosis using air-drying tech- nic. ATRA-treated group was predosed with ATRA by gavage 3 days before surgery. All rabbits were killed one week or four weeks after surgery. Using immunohistochemiscal staining, the liarvested target vesels were measured the protein expression of Cdk2 and proliferation cell nuclear antigen PCNA. Meanwhile vessel morphological measurement was taken for all target vessels. Resets （1） In normal group, Cdk2 and PCNA could not be detected in the target vessels. （2）In control group, there was a distinct intima hyperplasia and narrowed luminal area at six weeks after surgery. The expressions of PCNA and Cdk2 were significantly intense. （3） In A- TRA-treated group, the Cdk2 expression was markedly lower than that in control group. And there was an outstanding smaller infima/ media area ratio and larger luminal area in ATRA - treated group. （4） The PCNA expression and Cdk2 expression are in remarkable positive correlation. Conclusions ATRA could inhibit Cdk2 expression and VSMC proliferation, therefore it could reduce intima proliferation and elicit favorable geometric remodeling of the carotid atherosclerosis in rabbits.