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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 investigate the effects and mechanisms of all-trans retinoic acid (ARTA) on intimal hyperplasia, repair of neointimal hyperplasia and expression of CyclinD3 and LP-PLA2 in rabbit carotid arteries. Methods 54 healthy New Zealand white rabbits were randomly divided into 9 groups (n = 6): normal control group (A, B, C), high fat diet group (A, B, C) ). The normal control group only exposed the carotid artery after the normal diet; the high-fat diet group exposed the carotid artery and injured the intima; the treatment group was intragastrically administrated with ARTA, the other operation was the same as the high-fat diet group. After 1, 2 and 4 weeks after operation, the animals in groups A, B and C were sacrificed and morphological changes were observed and measured. The levels of LP-PLA2 in carotid artery intima-media and repair lesions were detected by ELISA and immunohistochemistry And CyclinD3 expression levels. Results ① The normal control group LP-PLA2 expression only slightly. CyclinD3 cytoplasm showed a weak positive expression, the nucleus was negative expression. ② In the high-fat diet group, the membrane started to proliferate within 7 days after operation, and proliferated significantly after 28 days. Foam cells, lipid streaks and stenosis were observed. LP-PLA2 and CyclinD3 expression levels were significantly higher than the normal group. ③ The expression levels of LP-PLA2 and CyclinD3 in the treatment group were significantly lower than those in the high-fat diet group (P <0.05). Intimal hyperplasia and luminal stenosis were significantly reduced (P <0.05). Conclusion ARTA can inhibit the hyperplasia and stenosis of carotid intima lesions by inhibiting the expression of LP-PLA2 and CyclinD3, inhibiting the inflammatory reaction in the intima and the proliferation of vascular smooth muscle cells.