摘要
目的检测过氧化物酶体增殖物激活受体(PPAR)γ激动剂及吡格列酮对血管紧张素Ⅱ(AngⅡ)诱导血管外膜成纤维细胞(AF)迁移的调节作用及机制。方法采用贴壁法培养SD大鼠胸主动脉AF。Tran-swell观察AngⅡ诱导AF迁移作用,RT-PCR检测AngⅡ1型受体(AT1R)mRNA水平。结果(1)AngⅡ刺激AF迁移呈浓度依赖性,当AngⅡ的浓度为10-7mol/L时,AF迁移数目最大(P<0·01);(2)PPARγ激动剂15D-PJG2和吡格列酮可抑制AngⅡ诱导AF迁移,并且呈剂量依赖性,浓度为10×10-6mol/L时作用最明显(P<0·01);(3)AT1R阻滞剂(氯沙坦)可完全抑制AngⅡ诱导的AF迁移(P<0·01),而AT2R阻滞剂(PD123319)对AF迁移无明显抑制作用(P>0·05);(4)与对照组相比,15D-PJG2和吡格列酮干预组AT1R mRNA表达水平呈剂量依赖性下降,浓度为10×10-6mol/L时抑制作用最明显(P<0·01)。结论PPARγ激动剂可抑制AngⅡ诱导的AF迁移,这可能是通过下调AFAT1R mRNA表达发挥作用。
Objective To investigate the effect and mechanism of peroxisome proliferators activated receptor （PPAR）γ agonists on migration of adventitial fibroblast（AF） by angiotensin Ⅱ （Ang Ⅱ ） induced. Methods AFs were isolated from rat thoracic aorta. The effect of Ang Ⅱ on AF migration was investigated by the method of transwell. AT1R mRNA level was detected by RT-PCR. Results （1）Ang Ⅱ stimulated AF migration in a dose-dependent manner. The maximal number of AF migration was occurred at Ang Ⅱ concentration of 10-7 mol/L（P〈0.01）. （2）PPARy agonists 15D-PJG2 and pioglitazone inhibited Ang Ⅱ induced AF migration dose dependently with maximal effect of 10×10^-6 mol/L（P〈0.01）. （3）AT1R blocker （losartan） completely abol- ished Ang Ⅱ induced AF migration（P〈0. 01）, whereas little effect by AT2 R blocker （PD123319） was shown（P〉0.05）. （4） 15D-PJG2 and pioglitazone downregulated AT1R mRNA level in AF in a dose-dependent manner with maximal effect at 10×10^-6 mol/L（P〈0.01）. Conclusion PPARy agonists 15D-PJG2 and pioglitazone in- hibit AF migration induced by Ang Ⅱ , which may be mediated by downregulating AT1R mRNA level.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2007年第7期561-564,共4页
Chinese Journal of Hypertension
