全反式维甲酸对兔颈动脉血管重塑及VEGF表达的影响

Effects of All-trans Retinoic Acid on Vascular Remodeling and VEGF Expression in Rabbit Carotid Artery after Endothelium Injury

目的探讨全反式维甲酸(atRA)对兔颈动脉内皮损伤后内膜增生、VEGF表达的影响及机制。方法新西兰雄性大白兔随机分为6组(n=6):治疗组(A、B)、对照组(A、B)、假手术组(A、B)。治疗组和对照组给予高脂饮食,手术损伤颈动脉内膜,治疗组给予atRA灌胃,假手术组手术但不损伤内膜。分别于术后7、28 d处死A、B组动物,取病变血管进行形态学观察,免疫组化测VEGF、PCNA表达水平。结果对照组术后7 d内膜开始增生,28 d时内膜增生明显,管腔狭窄,有粥样斑块形成,VEGF、PCNA表达明显增加。治疗组内膜增生较轻,28 d时内膜面积及斑块厚度低于对照组(分别为P<0.001、P<0.05),VEGF、PCNA阳性表达指数也低于对照组(分别为P<0.01、P<0.001)。结论atRA抑制兔颈动脉内皮损伤后VEGF、PCNA的表达,减轻新生内膜增殖及动脉粥样硬化病变形成。

Objective To evaluate the influence of all-trans retinoic acid （atRA） on intimal proliferation and VEGF expression in carotid endothelial injury in rabbits and its mechanisms. Methods 36 New Zealand rabbits were randomly divided into 6 groups： treatment group （A, B）, control group （A, B ）, sham-operation group （ A, B）. There were 6 rabbits in each group. The rabbits in the treatment groups and the control groups were fed with high cholesterol chow and subject to the carotid endothelial injury by air desiccation after 2 weeks. The sham-operation groups were fed with conventional chow, underwent surgery without endothelium injury. AtRA was administered daily to the treatment groups by gavages. The rabbits in the A groups and B groups were sacrificed respectively at 7 and 28 days after surgery. The carotid artery segments were harvested for histomorphometry observation. Immunohistochemistry were used to detect VEGF and PCNA protein. Results The VEGF and PCNA expression of control groups were significantly upregulated, neointimal formation was found in carotid artery at 7 days after injury and severe intima thickness, atherosclerosis was found at 28 days in the control group. In the treatment group, the intimal area, intimal/medial area ratio and maximum plague thickness of the artery at 28 days after surgery were lower than the control group, （P 〈0. 001 ; P 〈0. 001 ; P 〈0.05）, the expression of VEGF and PCNA were lower too（P 〈0. 01, P 〈0.001 respectively）. Conclusion The results indicate that atRA can suppress the VEGF and PCNA expression in endothelium injured artery, inhibit neointimal proliferation and atherosclerosis progression.