Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Department of Emergency and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
ACS Chem Neurosci. 2021 Aug 18;12(16):3002-3014. doi: 10.1021/acschemneuro.1c00059. Epub 2021 Aug 9.
Cerebral ischemia-reperfusion (CI/R) injury is a serious central nervous system disease. Propofol (PPF) exerts a neuroprotective effect in CI/R injury; the underlying cause is still unclear. Here, we cultured mouse hippocampal neuron (HT22 cells) in oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to mimic CI/R injury . PPF treatment promoted cell viability and reduced apoptotic cells in the OGD/R-treated HT22 cells, which was effectively abrogated by SNHG14 overexpression. Moreover, we constructed a CI/R injury mouse model on C57BL/6J mice by middle cerebral artery occlusion/reperfusion (MCAO/R), followed by administration of PPF. PPF reduced neuronal damage and loss, enhanced glial cell hyperplasia, and ameliorated cerebral cortex tissue damage and brain infarct in MCAO/R-induced mice. SNHG14 overexpression aggravated MCAO/R-induced CI/R injury in mice. Furthermore, SNHG14 promoted the expression of Atg5 and Beclin 1 via competitively binding miR-30b-5p, which contributed to activate autophagy and apoptosis in HT22 cells. In addition, the levels of p-p38 and p-SP1 were reduced in the OGD/R-treated HT22 cells in the presence of PPF. SP1 interacted with the promoter of SNHG14 and elevated the expression of SNHG14. PPF treatment inhibited the SP1-mediated up-regulation of SNHG14. In conclusion, this work demonstrates that PPF inhibits SNHG14 expression though the p38 MAPK signaling pathway. SNHG14 promotes Atg5 and Beclin 1 expression by sponging miR-30b-5p and thus activates autophagy and aggravates CI/R injury.
脑缺血再灌注（CI/R）损伤是一种严重的中枢神经系统疾病。异丙酚（PPF）在 CI/R 损伤中发挥神经保护作用；但其潜在原因仍不清楚。在这里，我们在氧葡萄糖剥夺/再氧合（OGD/R）条件下培养小鼠海马神经元（HT22 细胞），以模拟 CI/R 损伤。PPF 处理促进了 OGD/R 处理的 HT22 细胞中的细胞活力并减少了凋亡细胞，而过表达 SNHG14 则有效阻断了这一作用。此外，我们通过大脑中动脉闭塞/再灌注（MCAO/R）在 C57BL/6J 小鼠上构建了 CI/R 损伤模型，随后给予 PPF 治疗。PPF 减少了神经元损伤和丢失，增强了神经胶质细胞增生，并改善了 MCAO/R 诱导的小鼠大脑皮质组织损伤和脑梗死。SNHG14 的过表达加重了 MCAO/R 诱导的小鼠 CI/R 损伤。此外，SNHG14 通过竞争性结合 miR-30b-5p 促进了 Atg5 和 Beclin 1 的表达，从而促进了 HT22 细胞中的自噬和细胞凋亡。此外，在 OGD/R 处理的 HT22 细胞中，PPF 的存在降低了 p-p38 和 p-SP1 的水平。SP1 与 SNHG14 的启动子相互作用并提高了 SNHG14 的表达。PPF 处理抑制了 SP1 介导的 SNHG14 的上调。总之，这项工作表明，PPF 通过 p38 MAPK 信号通路抑制 SNHG14 的表达。SNHG14 通过海绵 miR-30b-5p 促进 Atg5 和 Beclin 1 的表达，从而激活自噬并加重 CI/R 损伤。
