Howard Florey Institute, Victoria, Australia.
J Neurotrauma. 2012 Apr 10;29(6):1243-8. doi: 10.1089/neu.2011.1824. Epub 2011 Dec 5.
Recent studies have demonstrated that angiotensin IV (Ang IV) provides protection against brain injury caused by cerebral ischemia. Ang IV is a potent inhibitor of insulin-regulated aminopeptidase (IRAP). Therefore, we examined the effect of IRAP gene inactivation on neuroprotection following transient middle cerebral artery occlusion (MCAo) in mice. IRAP knockout mice and wild-type controls were subjected to 2 h of transient MCAo using the intraluminal filament technique. Twenty-four hours after reperfusion, neurological deficits of the stroke-induced mice were assessed and infarct volumes were measured by TTC staining. The cerebral infarct volume was significantly reduced in the IRAP knockout mice compared to wild-type littermates with corresponding improvement in neurological performance at 24 h post-ischemia. An increase in compensatory cerebral blood flow during MCAo was observed in the IRAP knockout animals with no differences in cerebral vascular anatomy detected. The current study demonstrates that deletion of the IRAP gene protects the brain from ischemic damage analogous to the effect of the IRAP inhibitor, Ang IV. This study indicates that IRAP is potentially a new therapeutic target for the development of treatment for ischemic stroke.
最近的研究表明，血管紧张素 IV（Ang IV）可预防脑缺血引起的脑损伤。Ang IV 是胰岛素调节氨基肽酶（IRAP）的有效抑制剂。因此，我们研究了 IRAP 基因失活对小鼠短暂性大脑中动脉闭塞（MCAo）后神经保护的影响。采用管腔内纤维丝技术，使 IRAP 基因敲除小鼠和野生型对照小鼠经历 2 小时的短暂 MCAo。再灌注 24 小时后，评估卒中诱导小鼠的神经功能缺损，并通过 TTC 染色测量梗死体积。与野生型同窝仔相比，IRAP 基因敲除小鼠的脑梗死体积明显减少，缺血后 24 小时的神经功能也相应改善。在 IRAP 基因敲除动物中观察到 MCAo 期间补偿性脑血流增加，而脑血管解剖结构无差异。本研究表明，IRAP 基因缺失可保护大脑免受缺血性损伤，类似于 IRAP 抑制剂 Ang IV 的作用。这项研究表明，IRAP 可能是治疗缺血性中风的新治疗靶点。
