全反式维甲酸对兔颈动脉粥样硬化病灶VSMC增殖及AKT1表达影响.docVIP

全反式维甲酸对兔颈动脉粥样硬化病灶VSMC增殖及AKT1表达影响 作者：张青青 董果雄 张社华 【摘要】 目的 探讨全反式维甲酸(atRA)对兔颈动脉内膜损伤后内膜增生以及蛋白激酶B(AKT1)、增殖细胞核抗原（PCNA）表达的影响和机制。方法 新西兰雄性大白兔36只，随机分为6组：假手术A、B组,手术A、B组,手术并予atRA治疗A、B组（治疗A、B组），每组各6只。各组均给予高脂饮食14 d后，手术组作颈动脉内膜损伤模型。治疗组于术前3 d开始每天给予atRA灌胃，其余操作同手术组。假手术组手术但不损伤内膜。于术后7 d处死A组动物， 28 d处死B组动物。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，用免疫组化法检测粥样硬化病灶中AKT1、PCNA的表达水平。结果 手术组术后7 d内膜开始增生， 28 d时增生明显，粥样斑块形成，管腔狭窄，AKT1、 PCNA阳性表达明显。治疗组内膜增生较轻， 28 d时，内膜面积及斑块厚度低于手术组(t=3.797、3.704,Plt;0.01)，AKT1、PCNA阳性表达指数亦低于手术组(t=4.741、2.890,Plt;0.05)。结论atRA能抑制兔颈动脉内皮损伤后AKT1、PCNA的表达，抑制平滑肌细胞增殖，从而抑制内膜增生及动脉粥样硬化病变进程。 【关键词】 维甲酸；肌细胞,平滑肌；冠状动脉再狭窄；原癌基因蛋白质cakt 　　［ABSTRACT］ Objective To investigate the influence of alltrans retinoic acid (atRA) on intima proliferation and expressions of AKT1 and PCNA in rabbit carotid artery after endomembrane injury. Methods Thirtysix New Zealand rabbits wereevenly randomized to six groups: shamoperation group A and group B; operation group A and group B; and treatment group A and group B. All the rabbits were fed with high fat diet for 14 days. A model of carotid artery endomembrane injury was created in operation group. In treatment groups, rabbits were lavaged with atRA daily for 3 days before operation. Those in shamoperation groups underwent surgery without injuring the endomembrane. Rabbits in groups A were killed 7 days after operation and those in groups B, 28 days. Carotid specimens were taken for gross examination and immunohistochemistry study used for detection of the expressions of AKT1 and PCNA proteins. Results Seven days after operation, neointima formation was found in carotid artery in the operation group, and it became obvious afetr 28 days with atherosclerosis plaque, narrowing of arterial lumen and expressions of AKT1 and PCNA. In the treatment group, there was mild intima proliferation, and, 28 days after surgery, the intima area was smaller and the plague was thinner than that of the operation group (t=3.797, 3.704;Plt;0.01). The index