N-乙酰化-α-连接酸性二肽酶抑制剂对压力诱导缺血后的小鼠视网膜神经节细胞具有神经保护作用。

N-acetylated-alpha-linked-acidic dipeptidase inhibitor has a neuroprotective effect on mouse retinal ganglion cells after pressure-induced ischemia.

作者信息

Harada C, Harada T, Slusher B S, Yoshida K, Matsuda H, Wada K

机构信息

Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.

出版信息

Neurosci Lett. 2000 Oct 6;292(2):134-6. doi: 10.1016/s0304-3940(00)01444-0.

DOI:10.1016/s0304-3940(00)01444-0

PMID:10998567

Abstract

Excessive glutamate receptor activation is thought to be involved in the retinal ganglion cell (RGC) death after ischemic injury. In this study, we examined the effect of 2-PMPA (2-(phosphonomethyl)pentanedioic acid) on RGC survival in an ischemia-reperfusion model using C57BL/6 mouse eyes. 2-PMPA is a NAALADase (N-acetylated-alpha-linked-acidic dipeptidase) inhibitor, an enzyme responsible for the hydrolysis of the neuropeptide NAAG (N-acetyl-aspartyl-glutamate) to N-acetyl-aspartate and glutamate. 100mg/kg 2-PMPA were given with intraperitoneal injections 30 min before ischemia followed per hour injection for 3h. 2-PMPA increased surviving RGCs as well as retinal thickness after pressure-induced retinal ischemia. In addition, neuroprotection afforded by 2-PMPA was greater than that of N-methyl-D-aspartate receptor blocker. These data indicate that NAALADase inhibition may be useful in retinal disorders in which excessive amino acid transmission is pathogenic.

摘要

过量的谷氨酸受体激活被认为与缺血性损伤后视网膜神经节细胞（RGC）的死亡有关。在本研究中，我们使用C57BL/6小鼠眼睛的缺血再灌注模型，研究了2-磷酸甲基戊二酸（2-PMPA）对RGC存活的影响。2-PMPA是一种N-乙酰化-α-连接酸性二肽酶（NAALADase）抑制剂，该酶负责将神经肽N-乙酰天门冬氨酰谷氨酸（NAAG）水解为N-乙酰天门冬氨酸和谷氨酸。在缺血前30分钟腹腔注射100mg/kg的2-PMPA，随后每小时注射一次，共注射3小时。在压力诱导的视网膜缺血后，2-PMPA增加了存活的RGC数量以及视网膜厚度。此外，2-PMPA提供的神经保护作用大于N-甲基-D-天冬氨酸受体阻滞剂。这些数据表明，抑制NAALADase可能对氨基酸过度传递具有致病性的视网膜疾病有用。