All-trans retinoic acid reduces intimal thickening after balloon angioplasty in atherosclerotic rabbits

Objective To investigate the effects of oral administration of all trans retinoic acid (ATRA) on inhibition of intimal thickening after balloon angioplasty in the rabbit iliac artery atherosclerotic model. Methods Iliac atherosclerosis was induced in 24 rabbits, and balloon angioplasty was performed. At angioplasty, 24 rabbits were randomly divided into four groups (n=6 per group): Group 1: controls not receiving oral ATRA administration; Group 2: receiving oral ATRA (0.6 mg·kg 1 ·d 1 ) administration beginning 1 week prior to angioplasty and continuing for 4 weeks; Group 3: receiving oral ATRA (0.6 mg·kg 1 ·d 1 ) administration beginning immediately after angioplasty and continuing for 4 wk; Group 4: receiving oral ATRA (0.6 mg·kg 1 ·d 1 ) administration beginning 1 wk after angioplasty and continuing for 4 wk. Values of cross sectional area, ratio of intimal/medial area and thickness were determined by a computer based morphometric system, and cell proliferative activity was assessed by 3 H thymidine incorporation.Results Both the cross sectional area and the ratio of intimal/medial area and thickness were significantly reduced by ATRA administration compared with control group (P<0.01). The inhibitory effect is less potent when ATRA is administered 1 week before angioplasty. The ATRA inhibitory effect when administered 1 week after angioplasty is not different significantly form that when administered immediately after angioplasty. The 3H thymidine incorporation was also decreased in ATRA treated rabbits compared with controls (P<0.01). Conclusions Oral ATRA administration can be effective in inhibiting intimal thickening after balloon angioplasty. It is reasonable that ATRA should be administered immediately after angioplasty.

全反式维甲酸对兔颈动脉粥样硬化病变中Cdk2表达及血管平滑肌细胞增生的影响

目的探讨全反式维甲酸(ATRA)对兔颈动脉粥样硬化病灶中血管内膜的增生、血管平滑肌细胞(VSMCs)增殖、增殖细胞核抗原(PCNA)及细胞周期素依赖性激酶Cdk2表达规律的影响。方法36只新西兰雄性大白兔随机分为3组:正常饮食组、手术组、ARTA治疗组,每组12只。手术组和治疗组均给予高脂饮食,两周后用空气干燥法制作颈动脉内膜损伤模型,治疗组于术前3d开始给予ATRA灌胃。于术后1、4周处死动物,取病变血管应用HE染色、免疫组化和计算机图像分析法进行形态学、PCNA和Cdk2表达水平的检测。结果①正常动脉壁未见PCNA及Cdk2表达。②手术组在术后第1周时内膜开始增生,第4周增生明显,且出现泡沫细胞、脂质核心形成、管腔狭窄;增生内膜中Cdk2表达水平增高。③治疗组Cdk2的表达明显低于手术组(P<0.05),VSMCs的迁移、增殖、内膜增生和管腔狭窄显著减轻(P<0.05)。④PCNA表达与Cdk2表达呈显著正相关(P<0.01)。结论ARTA可通过抑制Cdk2表达,抑制VSMCs的迁移和增殖,从而抑制兔颈动脉粥样硬化新生内膜过度增生和管腔狭窄。

全反式维甲酸对颈动脉内膜损伤后MMP-2和TIMP-2表达的影响

目的观察全反式维甲酸(ATRA)对血管损伤后细胞外基质以及TIMP-2和MMP-2表达的影响。方法 36只新西兰大白兔随机分为正常对照组、模型组和ATRA干预组。分析动脉内膜增生、管腔狭窄和细胞外基质沉积情况,Western blot方法检测肺组织MMP-2和TIMP-2表达。结果内膜损伤后ATRA干预可抑制MMP-2蛋白表达,促进TIMP-2蛋白表达;ATRA干预组的内膜增生程度轻于模型组,血管新生内膜中细胞外基质沉积也明显减少(P<0.05)。结论 ATRA在血管内膜损伤早期能促进TIMP-2表达、抑制MMP-2表达,抑制细胞外基质沉积和平滑肌细胞迁移,抑制内膜过度增生。

全反式维甲酸防治经皮腔内冠状动脉成形术后再狭窄的研究进展

经皮腔内冠状动脉成形术 (PTCA)是目前治疗冠心病的有效措施之一 ,但术后 3 0～ 5 0 %病变血管再狭窄发生率 ,已严重地影响了 PTCA术后的远期疗效 ,临床上目前尚无有效预防 PTCA术后再狭窄发生的药物。全反式维甲酸 (ATRA)是一种具有广泛生物学效应维生素 A类衍生物 ,可明显抑制细胞增殖 ,近年来一些研究表明 ,该药在防治 PTCA术后再狭窄发生方面具有多种抑制作用 。

全反式维甲酸抑制兔颈动脉内皮损伤后内膜增殖和聚集素表达的研究

目的观察全反式维甲酸(atRA)对兔颈动脉内皮损伤后内膜增生、聚集素表达的影响,探讨atRA抗血管再狭窄的作用及机制。方法新西兰雄性大白兔36只,随机分为6组:治疗组(A、B)、对照组(A、B)、假手术组(A、B),每组6只。治疗组和对照组给予高脂饮食,2周后行颈动脉内膜空气干燥术,假手术组正常饮食,手术但不损伤内膜,治疗组术前3d开始atRA灌胃。分别于术后7、28d处死A、B组动物,取病变血管进行形态学观察,免疫组化检测聚集素、PCNA表达水平。结果对照组术后7d内膜开始增生,28d增生明显,管腔狭窄,有粥样斑块形成。治疗组内膜增生较轻,28d时内膜面积、内膜/中膜面积比、管腔狭窄度均低于对照组(P<0.01),聚集素、PCNA阳性表达低于对照组(P<0.05或<0.01)。结论 atRA抑制动脉内皮损伤后新生内膜增殖及动脉粥样硬化病变形成,抑制聚集素表达是机制之一。