Hao Wei, Wu Xi-qiang, Xu Rong-tian
Department of Radiology, The First Affiliated Hospital, China Medical University, Shen yang 110001, Liaoning Province, PR China.
Brain Res. 2009 Jul 28;1282:156-61. doi: 10.1016/j.brainres.2009.05.041. Epub 2009 May 22.
The study investigated the effect of aminoguanidine (AG) on inducible nitric oxide synthase (iNOS), aquaporin-4 (AQP4), malondialdehyde (MDA) and glutathione (GSH) levels in surgical brain injury (SBI) in rats. AG (75, 150 and 300 mg/kg, i.p.) was administered immediately following surgical resection. Using an SBI model, the absence of iNOS protein in any brain tested (sham-operated group, SBI group and SBI+AG group) at 24 h after SBI was confirmed by Western blot analysis. The expression of AQP4 protein in brain tissue at the edge of the resection site increased at 24 h after SBI, which could be greatly attenuated by the treatment with AG (150 mg/kg), while AG at the dose of 75 mg/kg or 300 mg/kg had no significant effect on it. In addition, there was a marked decrease of MDA values and a great increase of the GSH levels at 24 h after SBI in SBI+AG (150 mg/kg) group compared with SBI group. Whereas AG (300 mg/kg) elevated oxidative stress compared with SBI group. Our results indicate that the anti-edematous effect of AG observed in our study is dose-dependent and unlikely related to its inhibition effect on iNOS and may attribute to its roles on the regulation of AQP4 expression and antioxidative property at brain tissue after SBI.
该研究调查了氨基胍(AG)对大鼠手术性脑损伤(SBI)中诱导型一氧化氮合酶(iNOS)、水通道蛋白4(AQP4)、丙二醛(MDA)和谷胱甘肽(GSH)水平的影响。手术切除后立即腹腔注射AG(75、150和300mg/kg)。采用SBI模型,通过蛋白质印迹分析证实,在SBI后24小时,任何测试脑区(假手术组、SBI组和SBI+AG组)均不存在iNOS蛋白。SBI后24小时,切除部位边缘脑组织中AQP4蛋白的表达增加,AG(150mg/kg)治疗可使其显著减弱,而75mg/kg或300mg/kg剂量的AG对其无显著影响。此外,与SBI组相比,SBI+AG(150mg/kg)组在SBI后24小时MDA值显著降低,GSH水平显著升高。而AG(300mg/kg)与SBI组相比增加了氧化应激。我们的结果表明,在我们的研究中观察到的AG的抗水肿作用是剂量依赖性的,不太可能与其对iNOS的抑制作用有关,可能归因于其对SBI后脑组织AQP4表达的调节作用和抗氧化特性。