全反式维甲酸对兔颈动脉粥样硬化病灶中NF-κB、P-选择素及VCAM-1表达的影响

Effect of all-trans retinoic acid on the expression of NF-κB,P-selectin and VCAM-1 in atherosclerotic plaques in rabbits

目的观察全反式维甲酸(ATRA)对兔颈动脉粥样硬化病灶中内膜增殖和NF-κB、P-选择素及VCAM-1表达的影响。方法新西兰雄性大白兔随机分为9组(n=6):假手术组(A、B、C)、对照组(A、B、C)、治疗组(A、B、C)。假手术组给予普通饮食并分离暴露颈动脉但不损伤内膜;对照组给予高脂饮食,动脉内膜空气干燥术损伤颈动脉内膜;治疗组给予ATRA灌胃,其余操作同对照组。分别于术后7、14、28天处死A、B、C组动物,取病变血管进行形态学观察及测定,采用免疫组化法检测NF-κB、P-选择素及VCAM-1表达水平。结果①假手术组未见内膜增生,NF-κB及P-选择素仅有微量表达,未见VCAM-1表达;②对照组术后7天内膜开始增生,14、28天时内膜增生明显,管腔狭窄,管壁有粥样斑块形成,NF-κB、P-选择素及VCAM-1有多量表达;③治疗组内膜增生较轻,14和28天时内膜面积显著低于对照组(P均<0.05),NF-κB、P-选择素及VCAM-1阳性表达指数也显著低于对照组(P均<0.05)。结论 ATRA能明显抑制粥样硬化病灶中内膜增殖,其机制可能是通过抑制NF-κB的激活和表达,下调NF-κB的靶基因P-选择素及VCAM-1的表达从而抑制炎症过程。

Objective To observe the influence of all-trans retinoic acid（ATRA） on the process of neointimal formation and the expression of NF-κB,P-selectin and VCAM-1 in atherosclerotic plaques in rabbits. Methods New Zealand rabbits were randomly divided into 9 groups（n=6）： sham-operation groups（A,B,C）,control groups（A,B,C）,treatment groups（A,B,C）.There were 6 rabbits in each group.The sham-operation groups were fed with conventional chow,and underwent surgery without endothelium injury.The control groups were fed with high cholesterol chow and subjected to the carotid endothelial injury by air desiccation after 2 weeks.The treatment groups were administered ATRA daily by gavage,and other measures were the same as the control groups.The rabbits in the A,B and C groups were sacrificed respectively at 7,14 and 28 days after surgery.The carotid artery segments were harvested for histomorphometry observation and determination,and immunohistochemistry were used to detect the expression of NF-κB,P-selectin and VCAM-1. Results① In the sham-operation groups,neointimal formation was not found and the expression of NF-κB and P-selectin was microscale.The expression of VCAM-1 was not observed in these groups.② In the control groups,neointimal formation was found in carotid artery at 7 days after injury and severe intima thickness,atherosclerotic plaques in vessel wall was found at 14 and 28 days.The expression of NF-κB,P-selectin and VCAM-1 of control groups was detected.③ In the treatment groups,the intimal area and intimal/medial area ratio at 14 and 28 days after surgery were lower than those in the control groups（all P0.05）,and the expression of NF-κB,P-selectin and VCAM-1 was also lowered（all P0.05）. Conclusions The results showed that ATRA can inhibit neointimal formation in atherosclerotic plaques in rabbits,and the possible mechanism is that ATRA inhibits the acivation and expression of NF-κB,then decreases the expression of P-selectin and VCAM-1,which are regulated by NF-κB,thus it ultimately inhibits the inflammation.