微小RNA-8126介导的抗氧化应激减轻异氟烷对发育中大鼠海马的神经毒性
MicroRNA-8126-Mediated Antioxidant Stress Attenuates Isoflurane-Induced Hippocampal Neurotoxicity in Developing Rats.
作者信息
Pan Wen, Xiao WenFeng, Xue LingShuai, You Chao
机构信息
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610044, China.
Department of Neurosurgery, Sichuan Mianyang 404 Hospital, Mianyang 621053, Sichuan, China.
出版信息
Evid Based Complement Alternat Med. 2022 Aug 17;2022:1618577. doi: 10.1155/2022/1618577. eCollection 2022.
OBJECTIVE
To investigate the effect of microRNA-8126 () on isoflurane-induced hippocampal neurotoxicity in rats.
METHODS
A rat isoflurane nerve injury model was constructed. The expression of in the hippocampal region of normal and injured rats was measured by qRT-PCR; synaptic density protein-95, PAK-3 (p21-activated kinase-3) and apoptosis-related proteins cytochrome C, cleaved caspase-3, and cleaved PARP were detected by Western blot. The Cytochrome C, cleaved-caspase-3, and cleaved PARP expression was detected by WB, as well as GSH-Px, CAT, SOD, and ROS.
RESULTS
lowly expressed in the isoflurane-treated rat hippocampal region and in rat hippocampal neuronal cells, and the expression of apoptosis-related proteins and apoptosis levels were significantly increased, and neural activity, cell activity, and proliferation capacity were significantly decreased. Oxidative stress levels and ROS content were significantly increased; overexpression of in the rat hippocampal region significantly inhibited oxidative stress and apoptosis. Overexpression of in rat hippocampal neural progenitor cells significantly increased cell activity, proliferative capacity, and significantly smaller mitochondrial size and it decreased ROS content and oxidative stress levels and apoptosis-related protein expression compared to isoflurane-treated cells; while inhibition of expression in rat hippocampal neuronal cells significantly decreased cell activity, proliferative capacity, and mitochondrial size compared to the control group. In contrast, inhibition of miR-8126 expression in rat hippocampal neuronal cells resulted in a further decrease in cell activity, proliferation capacity, and significantly larger mitochondrial size and increased expression of apoptosis-related proteins compared with the control group. regulates the activity of rat hippocampal neuronal cells by targeting ATF4.
CONCLUSIONS
attenuates isoflurane-induced hippocampal neurotoxicity in rats by mediating antioxidative stress.
目的
探讨微小RNA - 8126（）对异氟烷诱导的大鼠海马神经毒性的影响。
方法
构建大鼠异氟烷神经损伤模型。通过qRT - PCR检测正常和损伤大鼠海马区中 的表达；通过蛋白质免疫印迹法检测突触密度蛋白 - 95、PAK - 3（p21激活激酶 - 3）以及凋亡相关蛋白细胞色素C、裂解的半胱天冬酶 - 3和裂解的聚（ADP - 核糖）聚合酶。通过蛋白质免疫印迹法检测细胞色素C、裂解的半胱天冬酶 - 3和裂解的聚（ADP - 核糖）聚合酶的表达，以及谷胱甘肽过氧化物酶、过氧化氢酶、超氧化物歧化酶和活性氧。
结果
在异氟烷处理的大鼠海马区和大鼠海马神经元细胞中低表达，凋亡相关蛋白的表达和凋亡水平显著增加，神经活性、细胞活性和增殖能力显著降低。氧化应激水平和活性氧含量显著增加；大鼠海马区中 的过表达显著抑制氧化应激和凋亡。大鼠海马神经祖细胞中 的过表达显著增加细胞活性、增殖能力，线粒体大小显著减小，与异氟烷处理的细胞相比，活性氧含量、氧化应激水平和凋亡相关蛋白表达降低；而抑制大鼠海马神经元细胞中 的表达与对照组相比，细胞活性、增殖能力和线粒体大小显著降低。相反，与对照组相比，抑制大鼠海马神经元细胞中miR - 8126的表达导致细胞活性、增殖能力进一步降低，线粒体大小显著增大，凋亡相关蛋白表达增加。 通过靶向激活转录因子4（ATF4）调节大鼠海马神经元细胞的活性。
结论
通过介导抗氧化应激减轻异氟烷诱导的大鼠海马神经毒性。
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