Department of Neurosurgery, Anhui No. 2 Provincial People's Hospital, Hefei, Anhui Province, China.
Clinical College, Anhui Medical University, Hefei, Anhui Province, China.
Eur J Neurosci. 2021 Nov;54(9):7318-7331. doi: 10.1111/ejn.15458. Epub 2021 Oct 7.
Ischemic stroke leads to severe neurological dysfunction in adults. Hyperbaric oxygen (HBO) induces tolerance to cReperfusion inj/reperfusion (I/R) injury. Therefore, our aims were to investigate whether SIRT1 participates in regulatingin the neuro-protective effect of HBO in a cerebral I/R model and its mechanism. Mice N2a cells were used to construct an oxygen deprivation/reperfusion (OGD/R) model to simulate in vitro brain I/R injury and to evaluate the role of HBO in OGD/R stimulated cells. Cell proliferation was detected using MTT, and apoptosis was determined by flow cytometry. ELISA was used to measure the concentration of TNF-α, IL-1β and IL-6 related inflammatory factors. RT-qPCR and western blot assays were performed to test the expression of SIRT1. Immunoprecipitation was used to detect acetylation of HMGB1. Expression of SIRT1 was obviously reduced after OGD/R treatment in N2a cells, while SIRT1 was obviously enhanced in HBO treated cells. Moreover, knockdown of SIRT1 induced neuro-inflammation damage in cells and HBO effectively improved the inflammatory response in OGD/R treated cells by affecting SIRT1 levels. Furthermore, HBO induced the deacetylation of HMGB1 via regulating SIRT1. Interestingly, HBO via regulating the SIRT1-induced HMGB1 deacetylation and suppressing MMP-9 improved ischemic brain injury. HBO regulated ischemic brain injury via regulation of SIRT1-induced HMGB1 deacetylation, making it a potential treatment for ischemic brain injury treatment.
缺血性中风会导致成年人严重的神经功能障碍。高压氧（HBO）诱导对再灌注损伤的耐受。因此，我们的目的是研究 SIRT1 是否参与调节 HBO 在脑 I/R 模型中的神经保护作用及其机制。使用 N2a 细胞构建氧剥夺/再灌注（OGD/R）模型，模拟体外脑 I/R 损伤，并评估 HBO 在 OGD/R 刺激细胞中的作用。MTT 检测细胞增殖，流式细胞术检测细胞凋亡。ELISA 检测 TNF-α、IL-1β 和 IL-6 相关炎症因子浓度。RT-qPCR 和 Western blot 检测 SIRT1 表达。免疫沉淀检测 HMGB1 的乙酰化。OGD/R 处理后 N2a 细胞中 SIRT1 表达明显降低，而 HBO 处理细胞中 SIRT1 明显增强。此外，SIRT1 敲低诱导细胞神经炎症损伤，HBO 通过影响 SIRT1 水平有效改善 OGD/R 处理细胞的炎症反应。此外，HBO 通过调节 SIRT1 诱导的 HMGB1 去乙酰化来诱导。有趣的是，HBO 通过调节 SIRT1 诱导的 HMGB1 去乙酰化和抑制 MMP-9 改善缺血性脑损伤。HBO 通过调节 SIRT1 诱导的 HMGB1 去乙酰化来调节缺血性脑损伤，使其成为缺血性脑损伤治疗的潜在治疗方法。
