Weuste Malte, Wurm Antje, Iandiev Ianors, Wiedemann Peter, Reichenbach Andreas, Bringmann Andreas
Paul Flechsig Institute of Brain Research, University of Leipzig Medical Faculty, Germany.
Biochem Biophys Res Commun. 2006 Aug 18;347(1):310-8. doi: 10.1016/j.bbrc.2006.06.077. Epub 2006 Jun 21.
We determined whether the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in the sensory rat retina alters during ischemia-reperfusion, and whether HB-EGF affects the osmotic swelling which is a characteristic feature of Müller glial cells after ischemia. Transient retinal ischemia was induced by elevation of the intraocular pressure for 1 h. Western blots revealed an upregulation of HB-EGF in the retina at 1, 3, and 7 days after reperfusion. HB-EGF inhibited the swelling of glial cells in retinal slices, via stimulation of the synaptic release of glutamate and subsequent activation of glial metabotropic glutamate receptors which resulted in an autocrine release of purinergic receptor agonists. Finally, activation of A1 receptors resulted in opening of glial K(+) and Cl(-) channels. It is suggested that the increased expression of HB-EGF and the inhibition of glial cell swelling may be parts of a protective role of HB-EGF in the ischemic retina.
我们确定了感觉性大鼠视网膜中肝素结合表皮生长因子样生长因子（HB-EGF）的表达在缺血再灌注期间是否发生改变，以及HB-EGF是否影响缺血后Müller神经胶质细胞的特征性渗透压肿胀。通过升高眼压1小时诱导短暂性视网膜缺血。蛋白质免疫印迹法显示，再灌注后1天、3天和7天视网膜中HB-EGF上调。HB-EGF通过刺激谷氨酸的突触释放以及随后激活神经胶质代谢型谷氨酸受体来抑制视网膜切片中神经胶质细胞的肿胀，这导致嘌呤能受体激动剂的自分泌释放。最后，A1受体的激活导致神经胶质K(+)和Cl(-)通道开放。提示HB-EGF表达增加和神经胶质细胞肿胀的抑制可能是HB-EGF在缺血性视网膜中的保护作用的一部分。
