罗格列酮对血管紧张素Ⅱ诱导的大鼠主动脉外膜成纤维细胞迁移的影响

Effects of rosiglitazone on rat aortic adventitial fibroblasts migration induced by angiotensinⅡ

目的:探讨PPARγ激动剂罗格列酮(ROSI)对血管紧张素Ⅱ(AngⅡ)诱导的大鼠主动脉外膜成纤维细胞(AFs)迁移的影响。方法:采用组织贴块法原代培养AFs并传代。取第5代纯化细胞用于实验,分为空白对照组、AngⅡ组、AngⅡ+0.1μmol/LROSI组、AngⅡ+1.0μmol/LROSI组、AngⅡ+10μmol/LROSI组,采用TranswellChamber测试细胞迁移。另取AFs分为4组:空白对照组、AngⅡ组、AngⅡ+10μmol/L ROSI组和AngⅡ+10μmol/L ROSI+GW9662组,用Western blotting检测基质金属蛋白酶2(MMP-2)蛋白的表达。另取AFs同上分为4组,采用明胶酶谱法检测MMP-2活性。结果:AngⅡ能促进AFs的迁移,ROSI可呈剂量依赖地抑制AFs的迁移(P<0.05)。ROSI能够降低AFs MMP-2蛋白的表达及MMP-2的活性。结论:ROSI可抑制AngⅡ诱导的大鼠AFs的迁移,其机制可能与抑制MMP-2的表达及活性有关。

Aim ： To explore the effect of PPARγ activators, rosiglitazone on the migration induced by angiotensin Ⅱ （Ang Ⅱ ） in cultured aortic adventitial fibroblasts （AFs）. Methods：AFs were prepared from rat aortas using explant technique and cultured for passages. The fifth passage cells were used. The AFs were allocated into 5 groups： control group, Ang Ⅱ group, Ang Ⅱ ＋ 0.1 μmol/L ROSI group, Ang Ⅱ ＋ 1.0 μmol/L ROSI group, and Ang Ⅱ ＋ 10 μmol/L ROSI group. Cell migration was determined by Transwell Chamber. Additionally, the AFs were allocated into 4 groups： control group, Ang Ⅱ group, Ang Ⅱ ＋ 10 μmol/L ROSI group, and Ang Ⅱ ＋ 10 μmol/L t/OSI ＋ GW9662 group. The expression and activity of MMP-2 were determined by Western blotting and zymography,respectively. Results： Ang Ⅱ significantly induced the migration of AFs, which was inhibited by pretreatment with rosiglitazone in a dose-dependent manner. Rosiglitazone could attenuate the expression of MMP-2 protein and the activity of MMP-2. Conclusion ： Rosiglitazone can obviously attenuate the expression and activity of MMP-2 induced by Ang Ⅱ , which may be realized by inhibiting the migration of AFs.