不同剂量瑞舒伐他汀对兔颈动脉粥样硬化斑块内CD147表达的影响

Impact of different dose rosuvastatin on the expression of CD147 in atherosclerotic plaque of rabbit

目的探讨不同剂量瑞舒伐他汀对兔颈动脉粥样硬化斑块内的CD147表达水平以及斑块稳定性的影响。方法将40只新西兰雄性大白兔随机分为五组:空白对照组、模型对照组(液氮损伤+高脂饲料建立动脉硬化模型)、低中高浓度药物干预三组(造模后分别予以瑞舒伐他汀1 mg·kg-1·d-1干预、2.5 mg·kg-1·d-1干预和5 mg·kg-1·d-1干预),15周后对兔颈总动脉血管进行病理形态学检查,反转录聚合酶链反应(RT-PCR)检测斑块内CD147 mRNA表达水平及蛋白质印迹法(Western blot)检测斑块内CD147蛋白表达水平。结果第15周末,模型对照组斑块内CD147 mRNA、CD147蛋白表达水平明显高于空白对照组(P<0.05)。病理显示模型对照组颈动脉内可见大量的不稳定斑块,模型对照组的8只兔中5只出现明显斑块破裂及血栓形成,而空白对照组的8只兔血管内膜光滑。瑞舒伐他汀干预,斑块内CD147 mRNA、CD147蛋白表达水平与模型对照组相比明显降低(P<0.05),且具有剂量依赖性,表现为高浓度药物干预组表达水平最低。病理显示瑞舒伐他汀干预后颈动脉动脉硬化斑块均较为稳定,动脉粥样斑块的面积明显减小,斑块纤维帽增厚,且具有剂量依赖性。结论兔颈动脉不稳定斑块内CD147的表达增多;瑞舒伐他汀能通过抑制CD147表达从而发挥其稳定动脉硬化斑块的作用,具有剂量依赖性。

Objective To elucidate the impact of different dose rosuvastatin on the stability of the plaque and the expression of CD147 in atherosclerotic plaque of rabbit. Methods Forty New Zealand white male rabbit were randomly divided into five groups： vacuity contrast group, model control group and rosuvastatin intervention group（1, 2.5, 5 mg·kg^-1·d^-1）. At fifteen weeks later, the carotid arteries in all groups were collected to undergo pathological examination. The CD147 mRNA and protein expression were respectively detected by RT-PCR and western blot at fifteen weeks later. Results Compared with vacuity contrast group, the expression level of CD147 mRNA and the CD147 protein in model control group significantly increased（P〈0.05）, and the plaques were also more unstable.It was found that plaque disruption and thrombosis occurred in 5 out of the 8 rabbits after triggering. Compared with the model control group, the expression level of CD147 mRNA and the CD147 protein in rosuvastatin treated group significantly decreased（P〈0.05）, the plaques were stable in drug intervention group, and this was a concentration-dependent fashion. Conclusion The expression of CD147 will significantly increase in unstable plaques and rosuvastatin can stabilize them by inhibiting the CD147 expression which is related to the rosuvastatin different dose. The anti-atherosclerosis effect of rosuvastatin might be partly achieved by this.