吡格列酮降低动脉粥样斑块破裂和血栓事件的实验研究  

A study of pioglitazone on reducing atherosclerosis plaque rupture and thrombosis

作　　者：赵学诚[1,2] 赵全明[1] 李德鹏[3] 刘瑜[4] 郑虹[1] 李丽琴[3] 张明多[1] 张玉慧[1] 闫云峰[1] 冯婷婷[1] 赵欣[1] 李昕禾 

机构地区：[1]首都医科大学附属安贞医院-北京市心肺血管病症研究所心内科十八病房,10029 [2]煤炭总医院 [3]中国人民解放军第二炮兵总医院PET/CT中心 [4]首都医科大学基础医学院

出　　处：《心肺血管病杂志》2016年第3期218-222,共5页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学基金(30972810,1370437);北京市自然科学基金(7132078)

摘　　要：目的：探讨吡格列酮是否具有改善斑块易损性,降低易损斑块的破裂率的作用及其可能机制。方法：将20只家兔随机分为两组：药物干预组（n=10）,对照组（n=10）。采用间断高脂饲养方法制造动脉粥样硬化模型,并进行斑块破裂激发试验。药物干预组于第1-18周在原饲料里添加吡格列酮（10 mg獉kg-1獉d-1）。于实验初期、中期、晚期分别留取血液标本进行MMP-9浓度测定。斑块破裂激发试验后处死动物,留取主动脉标本进行HE染色、巨噬细胞RAM-11及新生血管CD-31免疫组化染色,使用NIS-Elements AR Analysis病理图像分析系统分析斑块形态,测定斑块面积,进行巨噬细胞、新生血管计数。结果：实验中期及晚期,药物干预组血清（MMP-9）浓度均较对照组低[（2.25±0.11）vs.（2.60±0.19）,P=0.040;（2.27±1.17）vs.（2.70±0.37）,P=0.010]。实验晚期,药物干预组血清MMP-9浓度较对照组低[（2.27±1.17）vs.（2.70±0.37）,P=0.010]。斑块破裂激发试验后,药物干预组组血栓形成率较对照组明显减少（14.62%vs.39.07%,P=0.000）。与对照组相比,药物干预组斑块面积小[（0.029±0.018）vs.（0.186±0.093）,P=0.033]、巨噬细胞浸润少[（8.800±3.936）vs.（30.130±4.188）,P=0.003]、新生血管数量少[（80.267±13.094）vs.（162.637±73.112）,P=0.022]。结论：吡格列酮通过降低斑块内炎症程度提高斑块的稳定性,降低易损斑块的破裂率。Objective： We aimed at investigating the possibility of pioglitazone in reducing plaque vulnerability,and the underlying mechanism. Methods： 20 male New Zealand white rabbits were randomly divided into 2 groups： pioglitazone intervention group（ Group A,n = 10） and control group（ Group B,n = 10）. Atherosclerosis was induced in all rabbits by intermittent high-cholesterol diet and endothelial denudation. Pioglitazone（ 10 mg·kg- 1·d- 1） was added into the diet in Group A. Serum samples were obtained at 8 weeks and18 weeks for analysis of metabolic and MMP-9 concentration. After pharmacological triggering,all rabbits were euthanatized,and aortas were excised. All sections were stained with HE,of which macrophages and neovessels were stained with RAM-11 and CD-11 respectively. Then NIS-Elements AR Analysis was used for histopathological analysis. Results： Serum samples analysis showed both a lower MMP-9 concentration in pioglita-zone group at 8 weeks [（ 2. 25 ± 0. 11） vs.（ 2. 60 ± 0. 19）,P = 0. 040] and 18 weeks [（ 2. 27 ± 1. 17） vs.（ 2. 70 ± 0. 37）,P = 0. 010]. Histopathological examination demonstrated a significant decrease in plaque rupture and thrombosis in pioglitazone intervention group by chi-square test（ 14. 62% vs. 39. 07%,P = 0. 000）.Morphological assay showed plaque area was quite smaller in pioglitazone intervention group than control group[（ 0. 029 ± 0. 018） vs.（ 0. 186 ± 0. 093）,P = 0. 033]. Besides,macrophages[（ 8. 800 ± 3. 936） vs.（ 30. 130± 4. 188）,P = 0. 003]and neovessels [（ 80. 267 ± 13. 094） vs.（ 162. 637 ± 73. 112）,P = 0. 022] were also markedly reduced in pioglitazone intervention group compared with control group. Conclusion： Pioglitazone can decrease the incidence of plaque rupture and attenuate plaque vulnerability by ways of modulating vascular inflammation and inhibiting inflammatory progression.

关 键 词：吡格列酮 易损斑块 动脉粥样硬化 炎症 兔 

分 类 号：R54[医药卫生—心血管疾病]