TY -的A2 -穆里尔,巴勃罗盟,胡小盟——李案中盟——Doycheva Desislava遇到非盟-黄,Lei盟——Lenahan卡梅隆盟——刘,瑞盟——黄,胡安AU -高,凌AU - Tang Jiping AU -左,帮派AU -张约翰h . PY - 2020 DA - 2020/10/08 TI - Rh-CSF1变弱氧化应激和神经细胞凋亡通过CSF1R / PLCG2 / PKA / UCP2信号通路在新生儿HIE的老鼠模型SP - 6801587六世- 2020 AB -氧化应激(OS)和神经元细胞凋亡是主要病理过程缺血脑病(HIE)之后。集落刺激因子1 (CSF1)，结合CSF1受体(CSF1R)，已被证明可以减少缺氧缺血(HI)诱导的脑损伤后神经元的损失。在本研究中，我们假设CSF1可以通过CSF1R/PLCG2/PKA/UCP2信号通路减轻HI大鼠模型中os诱导的神经元变性和凋亡。共使用127只10日龄的Sprague Dawley幼鼠。HI由右颈总动脉结扎引起，随后暴露于缺氧2.5 h。在HI后1小时和24小时给予外源性重组人CSF1 (rh-CSF1)鼻腔注射。在HI诱导前1小时腹腔注射CSF1R抑制剂BLZ945或磷脂酶C-gamma 2 (PLCG2)抑制剂U73122。采用脑梗死体积测定、避悬崖试验、翻正反射试验、双免疫荧光染色、western blot、8-OHdG、MitoSOX染色、氟-玉C染色、TUNEL染色。我们的结果显示，HI后内源性CSF1、CSF1R、p-CSF1R、p-PLCG2、p-PKA和uncoupling protein2 (UCP2)的表达增加。 CSF1 and CSF1R were expressed in neurons and astrocytes. Rh-CSF1 treatment significantly attenuated neurological deficits, infarct volume, OS, neuronal apoptosis, and degeneration at 48 h after HI. Moreover, activation of CSF1R by rh-CSF1 significantly increased the brain tissue expressions of p-PLCG2, p-PKA, UCP2, and Bcl2/Bax ratio, but reduced the expression of cleaved caspase-3. The neuroprotective effects of rh-CSF1 were abolished by BLZ945 or U73122. These results suggested that rh-CSF1 treatment attenuated OS-induced neuronal degeneration and apoptosis after HI, at least in part, through the CSF1R/PLCG2/PKA/UCP2 signaling pathway. Rh-CSF1 may serve as therapeutic strategy against brain damage in patients with HIE. SN - 1942-0900 UR - https://doi.org/10.1155/2020/6801587 DO - 10.1155/2020/6801587 JF - Oxidative Medicine and Cellular Longevity PB - Hindawi KW - ER -