吡格列酮对粥样动脉硬化模型的斑块稳定性及新生血管形成的作用

Effects of pioglitazone on plaque stability and neovascularization in atherosclerotic plaque in rabbits

目的研究吡格列酮对粥样动脉硬化模型的斑块稳定性及新生血管形成的作用。方法选取新西兰白兔,按照体重随机分成实验组(20只)和模型组(20只);用高脂饲料喂养6周、普通的饲料喂养6周、高脂饲料再喂养4周的方法来建造动脉粥样的硬化模型;实验组,在高脂饲料开始的第1周,在高脂饲料里加入吡格列酮10 mg·kg^(-1),直到实验结束。在第8周和第18周,抽取血液样本,用生化试剂盒检测2组动物的高敏C反应蛋白(CRP)、血糖及血脂水平;用酶联免疫吸附试剂盒检测基质金属蛋白酶-9(MMP-9)水平。结果模型组与实验组巨噬细胞所占比例分别为(29.26±3.94)%,(8.78±4.01)%;这2组斑块的面积分别为(19.24±10.57)×10^(-2),(3.25±2.42)×10^(-2)mm^2;这2组新生血管数量分别为(163.03±72.96),(79.86±12.78)个,以上指标与模型组比较差异均有统计学意义(均P<0.05)。动物18F-FDG摄取:模型组与实验组中期SUVmean比值分别为0.80±0.08,0.64±0.06;这2组晚期SUVmean比值分别为1.02±0.60,0.50±0.12;这2组中期SUVmax比值分别为1.00±0.07,0.84±0.06;这2组晚期SUVmax比值分别为1.28±0.12,0.61±0.08,实验组的这3种SUV与模型组比较差异均有统计学意义(均P<0.05)。结论吡格列酮可减少斑块内部的炎症程度,加强斑块稳定性,减少新生血管的产生,减少易损斑块破损,从而起到抗动脉粥样硬化的作用。

Objective To study the effect of pioglitazone on plaque stability and neovascularization in atherosclerotic plaque. Methods New Zealand rabbits were selected and randomly divided into experimental group（n = 20） and model group（n = 20）. The atherosclerosis model by feeding high fat diet for 6 weeks,ordinary feed,high fat diet for 6 weeks and 4 weeks of feeding method to build atherosclerosis model. The first week of the experimental group were fed to the in the high fat diet with pioglitazone 10 mg · kg^-1,until the end of the experiment. In eighth weeks and eighteenth weeks,blood samples were taken. The hypersensitive C-reaction protein（CRP）,blood glucose,blood lipid in two groups were determined by biochemical detection kit. The level of matrix metalloproteinase-9（MMP-9） was detected by ELISA. Results The macrophage proportion in model group and the experimental group were（29. 26 ± 3. 94） %,（8. 78 ± 4. 01） %,the difference was statisticallysignificant（P〈0. 05）. The plaque area in model group and experimental group were（19. 24 ± 10. 57） × 10^-2,（3. 25 ± 2. 42） × 10^-2mm^2,the difference was statistically significant（P〈0. 05）. The number of neovascularization in model group and experiment group were 163. 03 ± 72. 96,79. 86 ± 12. 78,the difference was statistically significant（P〈0. 05）. Animal 18F-FDG uptake： average standard uptake（SUV mean） in model group and experimental group were 0. 80 ± 0. 08,0. 64 ± 0. 06,advanced SUVmean were 1. 02 ± 0. 60,0. 50 ± 0. 12,the differences were statistically significant（P〈0. 05）. Metaphase SUVmax in model group and experimental group were 1. 00 ± 0. 07,0. 84 ± 0. 06.Advanced SUVmax were 1. 28 ± 0. 12,0. 61 ± 0. 08,the differences were statistically significant（P〈0. 05）. Conclusion Pioglitazone can reduce the degree of inflammation in the plaque,strengthen the plaque stability,reduce the production of new blood vessels and reduce the damage of vulnerable plaques,thus play the role of anti-atherosclerosis.