Su Jingjing, Cui Mei, Tang Yuping, Zhou Houguang, Liu Ling, Dong Qiang
Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, People's Republic of China.
Biochem Biophys Res Commun. 2009 Oct 16;388(2):205-11. doi: 10.1016/j.bbrc.2009.07.135. Epub 2009 Aug 5.
Blood-brain barrier disruption and brain edema are detrimental in ischemic stroke. The kallikrein-kinin system appears to play an important role in the regulation of vascular permeability and is invoked in edema formation. The effects of kinins are mediated by bradykinin receptors B1R and B2R. However, little is known about the exact roles of bradykinin receptors in the early stage of cerebral ischemia. In this study, we demonstrated that ischemia upregulated the level of B1R and B2R at 24h after reperfusion by immunofluorescence assays, mainly expressed in astrocytes and neurons, respectively, in the ischemic penumbra. Moreover, B2R inhibition more effectively reduced neurological severity scores, blood-brain barrier permeability and cytokines release than B1R inhibition did. Additionally, B2R inhibition also significantly suppressed B1R protein level. Therefore, blockade of B2R may be a more effective strategy for the treatment of ischemic brain injury than B1R inhibition within 24h after reperfusion.
血脑屏障破坏和脑水肿在缺血性卒中中是有害的。激肽释放酶-激肽系统似乎在血管通透性调节中起重要作用，并与水肿形成有关。激肽的作用由缓激肽受体B1R和B2R介导。然而，关于缓激肽受体在脑缺血早期的确切作用知之甚少。在本研究中，我们通过免疫荧光分析证明，再灌注后24小时缺血上调了B1R和B2R的水平，它们分别主要在缺血半暗带的星形胶质细胞和神经元中表达。此外，与抑制B1R相比，抑制B2R能更有效地降低神经功能严重程度评分、血脑屏障通透性和细胞因子释放。此外，抑制B2R也显著抑制了B1R蛋白水平。因此，在再灌注后24小时内，阻断B2R可能是治疗缺血性脑损伤比抑制B1R更有效的策略。
