Department of Neonatology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Department of Pediatric, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Mol Cell Biochem. 2020 Sep;472(1-2):1-8. doi: 10.1007/s11010-020-03754-2. Epub 2020 Jul 6.
Hypoxic-ischemic (HI) brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. Autophagy is involved in the pathogenesis of HIBD. This study aims to investigate the effect of long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) on HIBD and to validate whether autophagy is involved in this process. A HIBD model in rat pups and a HI model in rat primary cerebrocortical neurons were established. Autophagy was evaluated by western blot. The HIBD in rats was evaluated by hematoxylin and eosin staining, TUNEL staining, triphenyl tetrazolium chloride staining, and morris water maze test. The HI injury in vitro was evaluated by determining cell viability and apoptosis. The results showed that CRNDE expression was time-dependently increased in the brain after HIBD. Administration with CRNDE shRNA-expressing lentiviruses alleviated pathological injury and apoptosis in rat hippocampus, decreased infarct volume, and improved behavior performance of rats subjected to HIBD. Furthermore, CRNDE silencing promoted cell viability and inhibited cell apoptosis in neurons exposed to HI. Moreover, CRNDE silencing promoted autophagy and the autophagy inhibitor 3-methyladenine counteracted the neuroprotective effect of CRNDE silencing on HI-induced neuronal injury both in vivo and in vitro. Collectively, CRNDE silencing alleviates HIBD, at least partially, through promoting autophagy.
缺氧缺血性（HI）脑损伤（HIBD）导致高新生儿死亡率和严重的神经发育障碍。自噬参与 HIBD 的发病机制。本研究旨在探讨长链非编码 RNA 结直肠肿瘤差异表达（CRNDE）对 HIBD 的影响，并验证自噬是否参与这一过程。建立了新生大鼠 HIBD 模型和原代大鼠皮质神经元 HI 模型。通过 Western blot 评估自噬。通过苏木精和伊红染色、TUNEL 染色、氯化三苯基四氮唑染色和 Morris 水迷宫试验评估大鼠的 HIBD。通过测定细胞活力和细胞凋亡评估体外 HI 损伤。结果显示，HIBD 后大鼠大脑中 CRNDE 的表达呈时间依赖性增加。给予 CRNDE shRNA 表达慢病毒可减轻大鼠海马区的病理损伤和细胞凋亡，减少梗死体积，改善 HIBD 大鼠的行为表现。此外，CRNDE 沉默促进了神经元暴露于 HI 后细胞的活力，并抑制了细胞凋亡。此外，CRNDE 沉默促进了自噬，自噬抑制剂 3-甲基腺嘌呤在体内和体外均拮抗了 CRNDE 沉默对 HI 诱导的神经元损伤的神经保护作用。总之，CRNDE 沉默通过促进自噬至少部分缓解了 HIBD。
