【摘要】 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）mm²,油红 O 染色阳性面积分别为（270±49）×10³、（150±35）×10³、（80±21）×10³μm²]。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。更多还原

【Abstract】 Objective To explore if PPARγ agonist rosiglitazone could enhance the anti- atherosclerotic effects of mouse peroxisome proliferator-activated receptor γ1（PPARγ1）gene transfer in apolipoprotein-knock out mice.Methods Adult ApoE-knock out mice were fed a Western-diet for 20-weeks and then injected with PBS,Ad.PPARγ1（5×10⁸ pfu）or Ad.GFP（5×10⁸ pfu）via jugular vein.Another group of mice were intervened with rosiglitazone(dissolved in 0.5% cellulose acetate,4 mg·kg^-1·d^-1, per gavage)1 week before Ad.PPARγ1 injection（n=10,each group）.Two weeks later,the lipid core and plaque composition were characterized with oil red O staining and Movat method respectively.The expression of PPARγ,SM-actin,MOMA-2,MMP-9/TIMP-1,CD40/CD40L and TF antigens in aortic roots and plaques among four groups were compared semi-quantitatively using immunohistochemical technology.Results All parameters were similar between AdGFP and PBS groups（P>0.05）.The area of plaque were significantly decreased and oil red O staining area significantly increased in AdPPARγ1[（0.86±0.12）mm²,（150± 35）×10³μm²]and AdPPARγ1 + RO[（0.79±0.15）mm²,（270±49）×10³μm²]treated mice compared with AdGFP group[（0.98±0.17）mm²,（80±21）×10³ μm²]all P<0.05.Elastic fiber, collagen and proteoglycan in plaques were also significantly increased in AdPPARγ1 and AdPPARγ1 + RO groups.Upregulation of PPARγ,SM-actin,TIMP-1 antigen activity and downregulation of MOMA-2,MMP-9, CD40/CD40L and TF antigen activity in AdPPARγ1 and most significantly in AdPPARγ1 + RO group were observed（P<0.05）.Conclusion Anti-atherosclerotic effects of PPARγ1 gene transfer in ApoE-knock out mice could be enhanced by PPARγ agonist rosiglitazone.更多还原