ARTA对兔颈动脉内膜损伤病灶CyclinD3及LP-PLA2的影响

Effect of Atra on the Expression of CyclinD3 and Lipoprotein-associated phospholipase A2 in injury nidus of carotid endothelium in rabbits

目的观察全反式维甲酸(ARTA)对兔颈动脉内膜损伤与修复病灶内膜增生和细胞周期素CyclinD3及炎性相关因子LP-PLA2表达的影响和机制。方法将54只健康新西兰大白兔随机分为9组(n=6):正常对照组(A、B、C)、高脂饮食组(A、B、C)、治疗组(A、B、C)。普通饮食后正常对照组仅暴露颈动脉;高脂饮食组,暴露颈动脉并损伤内膜;治疗组用ARTA灌胃,其他操作同高脂饮食组。术后1周、2周、4周处死A、B、C组动物,对病变血管行形态学观察和测定,分别用ELISA和免疫组化方法检测颈动脉内膜损伤与修复病灶中LP-PLA2和CyclinD3的表达水平。结果①正常对照组LP-PLA2仅有微量表达。CyclinD3胞浆呈弱阳性表达,胞核呈阴性表达。②高脂饮食组在术后7天内膜开始增生,28天后明显增生,出现泡沫细胞、脂质条纹、管腔狭窄。LP-PLA2和CyclinD3表达水平较正常组显著增高。③治疗组LP-PLA2和CyclinD3表达水平明显低于高脂饮食组(P<0.05)。内膜的增生和管腔的狭窄显著减轻(P<0.05)。结论ARTA可以通过抑制LP-PLA2和CyclinD3的表达,抑制内膜的炎症反应和血管平滑肌细胞的增生,从而抑制颈动脉内膜损伤病灶的过度增生和管腔狭窄。

Objective To observe the influence of all-trans retinoic acid（ATRA） on the process of neointimal formation and the expression of CyclinD3 and Lipoprotein-associated phos pholipase A2 in injury nidus of carotid endothelium in rabbits. Methods Fifty-six healthy male New-Zealand rabbits were randomly divided in to 9 groups（=6）：normal control groups（A,B,C）,high-fat groups（A,B,C）,treatment groups（A,B,C）.There were 6 rabbits in each group.The normal control groups were fed with conventional chow,and underwent surgery without endothelium injury.The high-fat groups were fed with high cholesterol chowand.subjected to the carotid endothelial injury by air desiccation.The treatment groups were administered ATRA daily by gavage,and other measures were the same as the high-fat 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 and ELISA were used respectively to detect the CyclinD3 and Lipoprotein-associated phos pholipase A2. Results ① In the normal control groups,neointimal formation was not found and the expression of LP-PLA2 was microscale.CyclinD3 could not be detected in the target vessels. ② In the high-fat groups,there was a distinct intima hyperplasia and narrowed luminal area at twenty-eight days after surgery. The expressions of CyclinD3 and LP-PLA2 were significantly intense. ③ In the treatment groups,the CyclinD3 and LP-PLA2 expression was markedly lower than that in high-fat group（P〈0.05）. And there was an outstanding smaller intimal/medial area ratio and larger luminal area in treatment groups（p〈0.05）. Conclusions The results showed that ATRA could inhibit LP-PLA2 and CyclinD3 expression, thus it could reduce inflammation and VSMC proliferation and inhibit intima proliferation and elicit favorable geometric remodeling of the injury nidus of carotid endothelium in rabbits.