全反式维A酸对兔动脉粥样硬化病灶中NF-κB和P-选择素表达的影响

Effects of all-trans retinoic acid on the expressions of NF-κB and P-selectin in atherosclerotic plaques in rabbits

目的通过观察全反式维A酸(ATRA)对兔颈动脉粥样硬化病灶中内膜增生、核因子κB(NF-κB)及P-选择素表达的影响,探讨其可能的抗炎机制。方法选择新西兰雄性大白兔54只,随机分为3组,每组18只,假手术组(A、B、C组,n=6)、对照组(A、B、C组,n=6,)、治疗组(A、B、C组,n=6)。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,行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 d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及P-选择素表达水平。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;(2)对照组术后7 d内膜开始增生,14、28 d时内膜增生明显,管腔狭窄,管壁有粥样斑块形成,NF-κB及P-选择素有多量表达;(3)治疗组内膜增生较轻,142、8 d时内膜面积及斑块厚度显著低于对照组(P<0.05),NF-κB及P-选择素阳性表达指数也显著低于对照组(P<0.05)。结论 ATRA能明显减轻动脉内膜损伤后病灶区域内膜增生,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-选择素的表达从而抑制炎症过程。

Objective By observing the influence of al1-trans retinoic acid（ATRA） on intimal proliferation and the expression of NF-κB and P-selecting in atherosclerotic plaques in rabbits to probe into the possible anti-inflammatory machanism.Methods 54 New Zealand rabbits were randomly divided into 3 groups：sham-operation groups（A,B,C）,contrast 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 contrast groups were fed with high cholesterol chow and subjected to 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 contrast groups.The rabbits in groups A,B and C were killed respectively after 7,14 and 28 days since the surgery.The carotid artery segments were harvested for histomorphometry observation and determination,and immunohistochemistry was used to detect the expressions of NF-κB and P-selectin.Results（1）The thickening of intima was not found in the sham-operation groups and the expressions of NF-κB and P-selecting was micro-scale.（2）In the contrast groups,the thickening of intima was found in carotid artery after 7 days since surgery,and severe thickening of intima and atherosclerotic plaques were found after 14,28 days.The expressions of NF-κB and P-selecting of contrast groups were significantly detected.（3）In the treatment groups,the intimal area,intimal/medial area ratio and maximum plague thickness of the artery after 14,28 days since the surgery were lower than the contrast groups（P0.05）,and the expressions of NF-κB and P-selecting were lower,too（P0.05）.Conclusion The results show that ATRA can inhibit neointimal formation after carotid endothelial injury in rabbits,and the possible mechanism is that ATRA inhibits the acivation and expression of NF-κB and then decreases the expression of P-selecting which is regulated by NF-κB and ultimately inhibits the inflammation.