辛伐他汀对不稳定斑块模型家兔血栓形成的影响

Effect of simvastatin on thrombosis in unstable plaque thrombosis rabbits model

关键词:  辛伐他汀  动脉粥样硬化  不稳定斑块  血栓形成

Key words:  simvastatin  atherosclerosis  plaque instability  thrombosis

摘要:

[目的] 探讨辛伐他汀对动脉粥样硬化(AS)不稳定斑块家兔模型血栓形成的影响。[方法] 将雄性新西兰家兔随机分两组,其中一组(假手术组)始终给予正常饮食,另一组给予高脂饲料喂养4周后,行腹主动脉球囊拉伤术,术后继续4周高脂饮食后转为正常饮食,并随机分为模型组和辛伐他汀组,辛伐他汀组给予辛伐他汀[10 mg/(kg·d)]灌胃4周,假手术组和模型组则给予等体积的生理盐水灌胃。各组家兔于药物干预4周后处死,处死前48 h和24 h两次行腹膜下注射蛇毒(0.15 mg/kg)和耳缘静脉注射组胺(0.02 mg/kg)药物触发斑块破裂。处死后取腹主动脉于体视镜下观察血栓形成情况,采用酶联免疫吸附法(ELISA法)检测血管性血友病因子抗原(vWF:Ag)和D-二聚体,放免法检测血栓素B2(TXB2)和6-酮-前列腺素F1α(6-keto-PGF1α)的浓度,并计算TXB2/6-keto-PGF1α的比值。[结果] 辛伐他汀干预4周后,体视显微镜下观察斑块部位血栓形成减少,与模型组相比差异有统计学意义(P<0.05),血浆vWF:Ag和 D-二聚体水平均降低,与模型组相比差异有统计学意义(P<0.01),血浆TXB2浓度降低、6-keto-PGF1α浓度升高,与模型组相比差异有统计学意义(P<0.05),TXB2/6-keto-PGF1α降低,与模型组相比差异有统计学意义(P<0.01).[结论] 辛伐他汀能够修复受损血管内皮细胞,改善血液高凝状态,抑制血小板聚集等,进而发挥抗血栓形成的作用,为辛伐他汀临床针对AS不稳定斑块患者,预防其血栓形成提供了实验依据。

Abstract:

[Objective] To investigate the effect of simvastatin on atherosclerotic plaque instability model of thrombosis in rabbits. [Methods] Male New Zealand rabbits were randomly divided into 2 groups. One group (sham group) was always given a normal diet. Another group was fed high-fat diet for four weeks, and then abdominal aortic endothelium was damaged by using 4F Forgarty catheter. The rabbits were replaced for normal diet until being sacrificed, and were randomly divided into model group and simvastatin group. Simvastatin group received simvastatin [10 mg/(kg·d)] for 4 weeks. Sham group and model group were given an equal volume of normal saline. Rabbits were sacrificed after 4 weeks of drug intervention in each group. Rabbits plaque rupture were triggered by giving intraperitoneal injections of venom under (0.15 mg/kg) and the ear vein injection of histamine (0.02 mg/kg) in 48 h and 24 h twice before sacrifice. Rabbits abdominal aortic thrombosis were observed in the stereo microscope after sacrifice. Rabbits were detected vWF and D-Dimer by ELISA, and were detected concentration of TXB2 and 6-keto-PGF1α by radioimmunoassay, and were calculated the ratio of TXB2/6-keto-PGF1α。 [Results] After four weeks of treatment with simvastatin, simvastatin group were observed to reduce plaque site thrombosis under stereo microscope, and there was a significant difference compared with the model group(P<0.01). Plasma levels of vWF: Ag and D-Dimer were lower in the simvastatin group, and there was a significant difference compared with the model group (P<0.01). Plasma concentration of TXB2 was lower and plasma concentration of 6-keto-PGF1α was higher, and there was a significant difference compared with the model group(P<0.05).The ratio of TXB2/6-keto-PGF1α was lower, and there was a significant difference compared with the model group(P<0.01). [Conclusion] Simvastatin can repair damaged endothelial cells and improve blood hypercoagulable state, inhibition of platelet aggregation, and thus play a role in anti-thrombosis. This study provides experimental evidence that simvastatin prevents thrombosis in the clinical for patients with AS unstabled plaque.