Gene transfer of PEDF attenuates ischemic brain damage in the rat middle cerebral artery occlusion model
Gene transfer of PEDF attenuates ischemic brain damage in the rat middle cerebral artery occlusion model
复制标题
DOI：
10.1111/j.1471-4159.2008.05529.x
复制
发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Yamada, Haruki
中科院分区：
文献类型：
--
作者：
Sanagi, Tomomi;Yabe, Takeshi;Yamada, Haruki
色素上皮衍生因子（PEDF）是一种50 kDa的糖蛋白，可保护各种类型的培养神经元免受神经毒性刺激，但其在CNS中的确切作用尚未完全了解。在这项研究中，我们使用的大鼠的大脑被转染过表达人PEDF，以阐明PEDF的神经保护作用后，短暂的大脑中动脉闭塞（MCAO）。一种含有人PEDF基因或E.于MCAO前70 min将大肠杆菌β-半乳糖苷酶（Ad.LacZ）直接注入大鼠右侧纹状体。与Ad. LacZ治疗组相比，Ad. PEDF治疗组的脑体积和水肿程度在MCAO后24 h显著减少。PEDF的过度表达减弱了由MCAO引起的神经元、星形胶质细胞和少突胶质细胞的变性。在Ad. PEDF注射的纹状体中，MCAO后促炎基因（TNF α、IL-1 β、IL-6、考克斯-2和iNOS）和水通道水通道蛋白4的上调显著降低。总之，本研究的结果提供了PEDF有效保护CNS神经元免受缺血性损伤的第一个体内证据，表明PEDF可能在CNS中具有内源性神经保护剂的作用。
Pigment epithelium-derived factor (PEDF) is a 50-kDa glycoprotein that protects various types of cultured neurons against neurotoxic stimuli, but its precise role in the CNS is not fully understood. In this study, we used rats whose brains were transfected to over-express human PEDF in order to elucidate the neuroprotective effect of PEDF following transient middle cerebral artery occlusion (MCAO). A replication-defective adenoviral vector containing the human PEDF gene (Ad.PEDF) or E. coli beta-galactosidase (Ad.LacZ) was directly injected into the right striatum at 7 days prior to 70 min of MCAO in rats. Infarct volume and degree of edema of the Ad.PEDF-treated group were significantly reduced compared to the Ad.LacZ-treated group 24 h after MCAO. Degeneration of neurons, astrocytes, and oligodendrocytes caused by MCAO were attenuated by over-expression of PEDF. The up-regulation of pro-inflammatory genes (TNF alpha, IL-1 beta, IL-6, COX-2, and iNOS) and water channel aquaporin 4 after MCAO was significantly reduced in Ad.PEDF-injected striatum. In conclusion, the results from this study provide the first in vivo evidence that PEDF is effective in protecting CNS neurons from ischemic insult, suggesting that PEDF may have a role as an endogenous neuroprotectant in the CNS.