Tianjin Medical University, Tianjin, PR China.
Neurosci Lett. 2010 Mar 26;472(3):179-83. doi: 10.1016/j.neulet.2010.02.002. Epub 2010 Feb 4.
Vascular endothelial growth factor (VEGF) is known to be an important stroke-related pathogenic factor for the formation of brain edema. We examined the therapeutic effect of human serum albumin on VEGF expression in acute ischemic stroke. Adult male Sprague-Dawley (SD) rats were subjected to Middle Cerebral Artery Occlusion (MCAO), the suture was withdrawn 2 h later, and 25% albumin (1.25 g/kg) or saline (5 ml/kg) was administered intravenously after reperfusion. The model was evaluated by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining, neurological deficits and brain water content. Serum albumin level was determined. VEGF expression was studied by enzyme linked immunosorbent assay (ELISA), quantitative real-time PCR and immunohistochemistry. We demonstrated that albumin administration maintained the serum albumin at a higher level than the sham group at 6 h, 1 d, 2 d and 3 d after MCAO, and significantly improved the neurological deficits and decreased the brain water content. In addition, the strong up-regulation of VEGF expression at 6 h and 1d after MCAO can be attenuated by albumin administration. However, albumin administration had no significant depressing effect on VEGF expression at 2 d, 3 d and 5 d after MCAO in the cortex and hippocampus. Strong up-regulation of VEGF immunoreactivity was noted in the saline group in the blood-brain barrier (BBB), and in neurons surrounding the peri-infarct area and periventricular area at 24 h after MCAO. The expression of VEGF in the albumin group was much weaker. Furthermore, there were high correlations between the brain water content with the serum albumin level, with serum VEGF protein level, and with brain VEGF mRNA expression at 24 h after MCAO. In conclusion, maintaining the serum albumin at a higher level, and attenuating endogenous VEGF expression at 6 h and 1d, but not 2 d, 3 d, or 5 d after MCAO, may partially contribute to the protective effects of albumin on reduction of brain edema in the early stage of ischemia.
血管内皮生长因子（VEGF）是一种与脑水肿形成有关的重要卒中致病因子。我们研究了人血清白蛋白对急性缺血性卒中 VEGF 表达的治疗作用。成年雄性 Sprague-Dawley（SD）大鼠接受大脑中动脉闭塞（MCAO），缝线在 2 小时后撤出，再灌注后静脉内给予 25%白蛋白（1.25 g/kg）或生理盐水（5 ml/kg）。通过 2,3,5-三苯基氯化四氮唑（TTC）染色、神经功能缺损和脑水含量评估模型。通过酶联免疫吸附试验（ELISA）、实时定量 PCR 和免疫组织化学研究 VEGF 表达。我们证明，与假手术组相比，白蛋白给药可使血清白蛋白在 MCAO 后 6 小时、1 天、2 天和 3 天维持在更高水平，并显著改善神经功能缺损和降低脑水含量。此外，白蛋白给药可减轻 MCAO 后 6 小时和 1 天 VEGF 表达的强烈上调。然而，在 MCAO 后 2 天、3 天和 5 天，白蛋白给药对皮质和海马区 VEGF 表达没有明显的抑制作用。MCAO 后 24 小时，在血脑屏障（BBB）和梗死周边区及脑室周围区的神经元周围，盐水组的 VEGF 免疫反应性明显上调。白蛋白组的 VEGF 表达较弱。此外，MCAO 后 24 小时，脑水含量与血清白蛋白水平、血清 VEGF 蛋白水平和脑 VEGF mRNA 表达之间存在高度相关性。总之，维持血清白蛋白处于较高水平，减轻 MCAO 后 6 小时和 1 天的内源性 VEGF 表达，但不减轻 MCAO 后 2 天、3 天或 5 天的表达，可能部分有助于白蛋白在缺血早期减轻脑水肿的保护作用。
