罗格列酮增加 apoE 基因敲除小鼠主动脉粥样硬化斑块的稳定性研究

Rosiglitazone promotes atherosclerotic plaque stability in apolipoprotein e-knockout mice

目的探讨罗格列酮对载脂蛋白 E(apoE)基因敲除小鼠主动脉粥样硬化斑块稳定性的影响及其可能机制。方法 32只6周龄 apoE 基因敲除小鼠随机分为罗格列酮组(18只)和对照组(14只),普通饮食14周后处死;切取小鼠主动脉根部制备石蜡切片,免疫组化法半定量测定两组粥样斑块内巨噬细胞、平滑肌细胞及炎性因子基质金属蛋白酶-9和肿瘤坏死因子-α的阳性率;Masson 法半定量观察两组胶原纤维的灰度变化。结果罗格列酮组巨噬细胞的阳性率较对照组显著降低[分别为(16.1±2.5)%和(36.2±6.8)%,P<0.05];平滑肌细胞的阳性率增加[分别为(38.5±7.2)%和(18.6±6.7)%,P<0.05];胶原纤维的灰度显著降低[分别为(169.4±1 5.4)和(21 5.5±14.6),P<0.05];基质金属蛋白酶9分别为(16.0±4.8)%和(33.6±9.7)%,P<0.05;肿瘤坏死因子-α的阳性率显著降低[分别为(15.9±2.9)%和(26.6±8.5)%,P<0.05]。结论罗格列酮可能通过下调局部炎性因子水平,改变斑块内的构成,稳定动脉粥样病变。

Objective To study the effect of rosiglitazone on plaque stability in ApoE-knockout mice. Methods Thirty-two 6-week-old ApoE-knockout mice were used as atherosclerosis models in two groups., rosiglitazone group （n= 18 ） and control group （n= 14 ）. Male and female mice were half separated into two groups. All mice were fed normal chow diet. Rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. The animals were sacrificed and aortae were prepared for analysis after fourteen weeks. Aortic root were cutted and prepared for paraffin section. The positive percentage of macrophage cells, smooth muscle cells, tumor necrosis factor-α and matrix metalloproteinase-9 in aortic lesions were measured by immunohistochemistry. The changes of grey gradient of collagen in lesion of both groups were measured by Masson stain. Results The positive percentage of smooth muscle cells [（ 38. 5 ± 7. 2 ）% vs （18. 6 ± 6.7）%, P 〈 0. 05] was significantly increased, and the positive percentage of macrophage cells [ （ 16.1 ± 2.5） % vs （36.2 ± 6.8） %, P〈 0. 05] and the grey gradient of collagen [（ 169. 4 ± 15.4） vs（ 215.5± 14.6）, P〈0. 05] was significantly decreased;the expression of tumor necrosis factor-α[（15.9±2.9） %vs （26. 6±8. 5）% ,P〈0. 05] and matrix metalloproteinase-9 [（ 16. 0 ± 4.8 ）% vs （ 33.6 ± 9. 7 ）%, P 〈 0. 05] were also significantly decreased in aortic lesion in rosiglitazone group compared with control group. Conclusions Rosiglitazone can increase the stability of atherosclerotic plaque by reducing the level of inflammatory cytokines and the amount of macrophage cells in lesions.