Aoki Yuto, Nakahara Tsutomu, Asano Daiki, Ushikubo Hiroko, Mori Asami, Sakamoto Kenji, Ishii Kunio
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences.
Biol Pharm Bull. 2015;38(2):321-4. doi: 10.1248/bpb.b14-00631.
Inhibitors of the mammalian target of rapamycin (mTOR) have been shown to protect against neuronal injury, but the mechanisms underlying this effect are not fully understood. The present study aimed to examine the effects of rapamycin, an inhibitor of the mTOR pathway, on inflammation and capillary degeneration in a rat model of N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity. Inflammation and capillary degeneration were evaluated by counting the numbers of CD45-positive leukocytes and Iba1-positive microglia, and by measuring the length of empty basement membrane sleeves, respectively. Marked increases in the numbers of leukocytes and microglia were observed 1 d after intravitreal injection of NMDA (200 nmol), and significant capillary degeneration was observed after 7 d. These NMDA-induced changes were significantly reduced by the simultaneous injection of rapamycin (20 nmol) with NMDA. These results suggest that rapamycin has preventive effects on inflammation and capillary degeneration during retinal injury.
雷帕霉素哺乳动物靶点（mTOR）抑制剂已被证明可预防神经元损伤，但其作用机制尚未完全明确。本研究旨在探讨mTOR通路抑制剂雷帕霉素对N-甲基-D-天冬氨酸（NMDA）诱导的大鼠视网膜神经毒性模型中炎症和毛细血管变性的影响。分别通过计数CD45阳性白细胞和Iba1阳性小胶质细胞的数量以及测量空基底膜套的长度来评估炎症和毛细血管变性。玻璃体内注射NMDA（200 nmol）后1天观察到白细胞和小胶质细胞数量显著增加，7天后观察到明显的毛细血管变性。同时注射雷帕霉素（20 nmol）与NMDA可显著减轻这些NMDA诱导的变化。这些结果表明，雷帕霉素对视网膜损伤期间的炎症和毛细血管变性具有预防作用。
