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目的探讨过氧化物酶体增殖剂活化受体(PPAR)γ活化剂马来酸罗格列酮能否增强腺病毒介导的 mPPARγ1基因转染抗 ApoE-/-小鼠动脉粥样硬化的作用。方法将20周龄ApoE-/-小鼠高脂饲养20周后随机分成4组(每组 n=10),即 AdPPARγ1组、AdPPARγ1+RO 组(病毒干预前1周予罗格列酮4 mg·kg~(-1)·d~(-1)灌胃)、AdGFP 组和 PBS 组。转染2周后比较各组小鼠主动脉根部斑块面积均值。Movat 5色套染法和油红 O 染色分析主动脉根部斑块成分变化。检测斑块内 PPARγ、血管平滑肌细胞(SM-actin)、巨噬细胞(MOMA-2)、MMP-9/TIMP-1、CD40/CD40L 和组织因子(TF)等抗原的免疫活性。结果 PBS 组与 AdGFP 组比较,各项指标差异均无统计学意义。与AdGFP 组比较,AdPPARγ1组和 AdPPARγ1+RO 组 ApoE-/-小鼠主动脉根部斑块面积和脂质含量减少(P<0.05)[AdGFP 组、AdPPARγ1组和 AdPPARγ1+RO 组病变面积均值分别为(0.98±0.17)、(0.86±0.12)、(0.79±0.15)mm~2,油红 O 染色阳性面积分别为(270±49)×10~3、(150±35)×10~3、(80±21)×10~3μm~2]。Movat 染色法显示 PBS 组和 AdGFP 组小鼠主动脉根部斑块成分差异不显著,而 AdPPARγ1组和 AdPPARγ1+RO 组纤维帽较厚、弹性纤维、胶原和蛋白聚糖含量增加。与 AdGFP组比较,AdPPARγ1组和 AdPPARγ+RO 组主动脉根部斑块 PPARγ、SM-actin、TIMP-1抗原免疫活性增强,而 MOMA-2、MMP-9、CD40/CD40L 和 TF 抗原免疫活性减弱,其中 AdPPARγ1+RO 组作用最显著。结论腺病毒介导的 mPPARγ1基因转染遏制 ApoE-/-小鼠动脉粥样硬化进程,促进动脉粥样硬化斑块向稳定表型转换,PPARγ活化剂马来酸罗格列酮增强上述作用。
Objective To investigate whether peroxisome proliferator-activated receptor (PPAR) γ activator rosiglitazone maleate can enhance the effect of adenovirus-mediated atherosclerosis of mPPARγ1 gene transfection against ApoE - / - mice. . Methods 20 weeks old ApoE - / - mice were fed with high fat for 20 weeks and divided into 4 groups (n = 10 in each group), AdPPARγ1 group, AdPPARγ1 + RO group (1 mg pretreatment with rosiglitazone 4 mg · kg ~ (-1) · d ~ (-1)), AdGFP group and PBS group. After 2 weeks of transfection, the average aortic root plaque area of each group was compared. Movat 5 color set method and oil red O staining analysis of aortic root plaque composition changes. The immunological activities of antigens such as PPARγ, SM-actin, MOMA-2, MMP-9 / TIMP-1, CD40 / CD40L and tissue factor (TF) Results Compared with AdGFP group, there was no significant difference in each index between PBS group and AdGFP group. Compared with AdGFP group, the aortic root plaque area and lipid content in AdPPARγ1 group and AdPPARγ1 + RO group decreased (P <0.05). The mean area of lesions in AdGFAR group, AdPPARγ1 group and AdPPARγ1 + RO group were (0.98 ± 0.17), (0.86 ± 0.12) and (0.79 ± 0.15) mm ~ 2, respectively. The positive area of oil red O staining was (270 ± 49) × 10-3 and (150 ± 35) × 10-3, 80 ± 21) × 10 ~ 3μm ~ 2]. Movat staining showed that there was no significant difference in the contents of plaque in the aorta between PBS group and AdGFP group. The fibrous cap was thicker and the content of elastic fiber, collagen and proteoglycan were increased in AdPPARγ1 group and AdPPARγ1 + RO group. Compared with AdGFP group, the immunological activities of PPARγ, SM-actin and TIMP-1 antigen in the aortic root plaque increased in AdPPARγ1 group and AdPPARγ + RO group, while the immunostimulatory activity of MOMA-2, MMP-9, CD40 / Among them, AdPPARγ1 + RO group had the most significant effect. Conclusion Adenovirus-mediated transfection of mPPARγ1 inhibits atherosclerosis in ApoE - / - mice and promotes the conversion of atherosclerotic plaque to stable phenotype. Rosiglitazone maleate, a PPARγ-activator, enhances these effects.