Oku Hidehiro, Morishita Seita, Horie Taeko, Nishikawa Yuko, Kida Teruyo, Mimura Masashi, Kojima Shota, Ikeda Tsunehiko
Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
Jpn J Ophthalmol. 2017 Mar;61(2):195-203. doi: 10.1007/s10384-016-0493-6. Epub 2016 Dec 28.
To determine whether P7C3-A20, a proneurogenic neuroprotective agent, can protect the retinal ganglion cells (RGCs) of rats from optic nerve crushing.
The left optic nerve of 67 rats was crushed, and 5.0 mg/kg/day of P7C3-A20 (crush-P7C3) or its vehicle (crush-placebo) was injected intraperitoneally for 3 days from one day prior to the crushing. The protective effects were determined by the number of Tuj-1-stained RGCs and by the ratio of the mRNA levels of BAX/Bcl-2 on day 7. The levels of NAD and NAD-related genes were also determined.
The density of RGCs was 2009.4 ± 57.7 cells/mm in the sham controls; it was significantly lower in the crush-placebo group at 979.7 ± 144.3 cells/mm (P < 0.0001). The neuroprotective effects of P7C3-A20 was demonstrated by the significantly higher density of 1266.0 ± 193.1 cells/mm than in the crush-placebo group (P = 0.01, Scheffe). After crushing the optic nerve the BAX/Bcl-2 ratio was higher in the optic nerves and retina, application of P7C3-A20 significantly reduced this ratio. P7C3-A20 significantly increased the NAD level in the untouched optic nerves from 1.36 ± 0.05 to 1.59 ± 0.10 nmol/mg protein (P = 0.02, t test). Crushing the optic nerve decreased the level to 1.27 ± 0.21 nmol/mg protein and P7C3-A20 preserved the level at 1.43 ± 0.10 nmol/mg protein. Crushing the optic nerve decreased the mRNA levels of Nampt and Sirt-1 in the optic nerves, while P7C3-A20 significantly restored the levels.
P7C3-A20 can protect RGCs from optic nerve crushing possibly through preserving the NAD levels in the optic nerves.
确定一种促神经生成的神经保护剂P7C3 - A20是否能保护大鼠视网膜神经节细胞（RGCs）免受视神经挤压损伤。
对67只大鼠的左侧视神经进行挤压，从挤压前一天开始，每天腹腔注射5.0 mg/kg的P7C3 - A20（挤压 - P7C3组）或其溶剂（挤压 - 安慰剂组），连续注射3天。在第7天，通过Tuj - 1染色的RGCs数量以及BAX/Bcl - 2 mRNA水平的比值来确定保护效果。同时也测定了NAD及与NAD相关基因的水平。
假手术对照组中RGCs的密度为2009.4±57.7个细胞/mm；挤压 - 安慰剂组显著降低至979.7±144.3个细胞/mm（P < 0.0001）。P7C3 - A20具有神经保护作用，其RGCs密度显著高于挤压 - 安慰剂组，为1266.0±193.1个细胞/mm（P = 0.01，谢费检验）。视神经挤压后，视神经和视网膜中的BAX/Bcl - 2比值升高，应用P7C3 - A20可显著降低该比值。P7C3 - A20使未受挤压的视神经中的NAD水平从1.36±0.05显著升高至1.59±0.10 nmol/mg蛋白（P = 0.02，t检验）。视神经挤压使NAD水平降至1.27±0.21 nmol/mg蛋白，而P7C3 - A20将其维持在1.43±0.10 nmol/mg蛋白水平。视神经挤压使视神经中Nampt和Sirt - 1的mRNA水平降低，而P7C3 - A20可显著恢复这些水平。
P7C3 - A20可能通过维持视神经中的NAD水平来保护RGCs免受视神经挤压损伤。
