Department of Anesthesiology, Capital Medical University Affiliated Beijing Friendship Hospital, 95 Yong-an Road, Xicheng District, Beijing, 100050, China.
Tsinghua Laboratory of Brain and Intelligence, Tsinghua University, 30 Shuangqing Road, Haidian District, Beijing, 100084, China.
Neurosurg Rev. 2023 Aug 29;46(1):213. doi: 10.1007/s10143-023-02125-x.
The purpose of the study is to explore the underlying mechanisms of xenon (Xe) which protects against spinal cord ischemia/reperfusion injury (SCIRI). A SCIRI rat model was induced by abdominal artery occlusion for 85 min and reperfusion. Xe postconditioning (50% Xe) was administered 1 h after 1 h of reperfusion. At reperfusion time points (2, 4, 6, and 24 h), rats were treated with spinal cord scans by MRI to assess the time of peak spinal cord injury after SCIRI. Subsequently, endoplasmic reticulum (ER) stress inhibitor sodium 4-phenylbutyrate (4-PBA) was administered by daily intraperitoneal injection (50 mg/kg) for 5 days before SCIRI. At 4 h after reperfusion, motor function, immunofluorescence staining, hematoxylin and eosin (HE) staining, Nissl staining, TUNEL staining, real-time reverse transcription polymerase chain (RT-PCR) reaction, and western blot analyses were performed to investigate the protective effects of Xe against SCIRI. In the rat I/R model, spinal cord edema peaked at reperfusion 4 h. SCIRI activated ER stress, which was located in neurons. Xe postconditioning remarkably alleviated hind limb motor function, reduced neuronal apoptosis rate, increased the number of normal neurons, and inhibited the expression of ER stress-related protein in spinal cord. Furthermore, the administration of the ER stress inhibitor 4-PBA strongly decreased ER stress-induced apoptosis following SCIRI. Xe postconditioning inhibits ER stress activation, which contributes to alleviate SCIRI by suppressing neuronal apoptosis.
本研究旨在探讨氙气（Xe）对脊髓缺血再灌注损伤（SCIRI）的保护作用的潜在机制。采用腹主动脉夹闭 85 分钟再灌注的方法建立 SCIRI 大鼠模型。Xe 后处理（50%Xe）在再灌注 1 小时后进行。在再灌注时间点（2、4、6 和 24 小时），通过 MRI 对大鼠脊髓进行扫描，以评估 SCIRI 后脊髓损伤的峰值时间。随后，在 SCIRI 前 5 天每天通过腹腔注射给予内质网（ER）应激抑制剂苯丁酸钠（4-PBA，50mg/kg）。在再灌注后 4 小时，进行运动功能、免疫荧光染色、苏木精和伊红（HE）染色、尼氏染色、TUNEL 染色、实时逆转录聚合酶链反应（RT-PCR）反应和 Western blot 分析，以研究 Xe 对 SCIRI 的保护作用。在大鼠 I/R 模型中，脊髓水肿在再灌注 4 小时时达到峰值。SCIRI 激活了位于神经元中的 ER 应激。Xe 后处理显著改善了后肢运动功能，降低了神经元凋亡率，增加了正常神经元的数量，并抑制了脊髓中 ER 应激相关蛋白的表达。此外，内质网应激抑制剂 4-PBA 的给药强烈降低了 SCIRI 后 ER 应激诱导的凋亡。Xe 后处理抑制 ER 应激激活，通过抑制神经元凋亡从而减轻 SCIRI。
