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匹诺塞林抑制血管紧张素Ⅱ收缩的大鼠主动脉环Rho激酶活性

Rho kinase inhibition activity of pinocembrin in rat aortic rings contracted by angiotensin II

  • 摘要: 目的:探讨匹诺塞林对血管紧张素Ⅱ(Ang Ⅱ)引起的血管收缩的作用及可能的分子机制。方法:在大鼠去内皮胸主动脉环中检测血管张力。Western blot用于分析肌球蛋白轻链磷酸酶调节亚单位1(MYPT1)磷酸化水平,Rho激酶1(ROCK1)和血管紧张素Ⅱ-1型受体(AT1R)蛋白表达水平。结果:匹诺塞林剂量依赖性地引起血管紧张素Ⅱ(100 nmol·L-1)收缩的去内皮动脉环的舒张效应。匹诺塞林在25及100 μmol·L-1时,明显减少血管紧张素Ⅱ诱导的MYPT1的磷酸化,并显著抑制血管紧张素Ⅱ引起的去内皮动脉环ROCK1蛋白的表达上调。同时结果显示匹诺塞林对血管紧张素Ⅱ作用的去内皮动脉环AT1R蛋白表达无影响。结论:匹诺塞林抑制血管紧张素Ⅱ引起的去内皮动脉环收缩,其部分机制与阻断RhoA/ROCK通路有关。

     

    Abstract: AIM:To investigate the effects of pinocembrin on angiotensin II(Ang II)-induced vascular contraction,and to explore its molecular mechanism of actions.METHODS:The isometric vascular tone was measured in rat thoracic aortic rings with denuded endothelium.Phosphorylation level of myosin phosphatase target unit 1(MYPT1),and protein levels of Rho kinase 1(ROCK1,ROKβ or p160ROCK) and angiotensin II type-1 receptor(AT1R) were determined by Western blot analysis.RESULTS:Pinocembrin produced a relaxant effect on endothelium-denuded aortic rings contracted by Ang II(100 nmol·L-1) in a dose-dependent manner.In endothelium-denuded aortic rings stimulated by Ang II,pretreatment with pinocembrin(25 and 100 μmol·L-1) for 20 min significantly attenuated MYPT1 phosphorylation and ROCK1 protein levels.Meanwhile,the protein level of AT1R in response to Ang II was not affected by pinocembrin in rat aortic rings.CONCLUSION:These findings indicate that pinocembrin inhibits vasoconstriction induced by Ang II in rat endothelium-denuded aortic rings,and the mechanism at least in part,is due to the blockade of the RhoA/ROCK pathway.

     

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