Liraglutide, one of the glucagon-like peptide 1 receptor (GLP-1R) agonists, has been demonstrated to protect brain damage produced by ischemic stroke. However, it remains unknown whether liraglutide attenuates early brain injury after subarachnoid hemorrhage. The present study was performed to explore the effect of liraglutide on early brain injury after subarachnoid hemorrhage in rats, and further investigate the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation, then received subcutaneous injection with liraglutide (50 or 100 μg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, and Evans Blue extravasation were measured 24 h after SAH. Immunofluorescent staining was performed to detect the extent of microglial activation in rat brain 24 h after SAH. TUNEL staining was performed to evaluate neuronal apoptosis in rat brain of SAH. Expression of GLP-1R, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), Bcl-2, Bax, and cleaved caspase-3 in rat brain were determined by western blot. Expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat brain was assessed by ELISA. Neurological dysfunction, brain water content, Evans Blue extravasation, microglial activation, and neuronal apoptosis were significantly reduced by GLP-1R agonist liraglutide. Expression of GLP-1R in rat brain was decreased after SAH, which is significantly elevated by liraglutide. Expression of inflammatory mediates like COX-2, iNOS, TNF-α, and IL-1β was increased after SAH, which were significantly inhibited by liraglutide. Furthermore, SAH caused the elevated expression of pro-apoptotic factors Bax and cleaved caspase-3 in rat brain, both of which were inhibited by liraglutide. In addition, liraglutide reversed the expression of anti-apoptotic protein Bcl-2. Our results demonstrated that liraglutide reduces early brain injury and attenuates inflammatory reaction and neuronal apoptosis in rats of SAH. Liraglutide provides neuroprotection against SAH, which might be associated with the inhibition of inflammation and apoptosis.

利拉鲁肽是胰高血糖素样肽 1 受体 (GLP-1R) 激动剂之一，已被证明可以保护缺血性中风引起的脑损伤。然而，利拉鲁肽是否能减轻蛛网膜下腔出血后的早期脑损伤仍不清楚。本研究旨在探讨利拉鲁肽对大鼠蛛网膜下腔出血后早期脑损伤的影响，并进一步探讨其潜在机制。Sprague-Dawley 大鼠通过血管内穿孔发生蛛网膜下腔出血 (SAH)，然后在 SAH 2 和 12 小时后皮下注射利拉鲁肽（50 或 100 μg/kg）或载体。在 SAH 后 24 小时测量 SAH 分级、神经系统评分、脑水含量和 Evans Blue 外渗。进行免疫荧光染色以检测 SAH 后 24 小时大鼠脑中小胶质细胞活化的程度。进行TUNEL染色以评估SAH大鼠脑中的神经元凋亡。通过蛋白质印迹法测定大鼠脑中 GLP-1R、环氧合酶-2 (COX-2)、诱导型一氧化氮合酶 (iNOS)、Bcl-2、Bax 和裂解的 caspase-3 的表达。通过ELISA评估大鼠脑中肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达。GLP-1R 激动剂利拉鲁肽显着降低了神经功能障碍、脑含水量、伊文思蓝外渗、小胶质细胞激活和神经元凋亡。SAH后大鼠脑中GLP-1R的表达降低，利拉鲁肽显着升高。SAH后炎症介质如COX-2、iNOS、TNF-α和IL-1β的表达增加，利拉鲁肽显着抑制。此外，SAH导致大鼠脑中促凋亡因子Bax和cleaved caspase-3的表达升高，两者均被利拉鲁肽抑制。此外，利拉鲁肽逆转了抗凋亡蛋白 Bcl-2 的表达。我们的研究结果表明，利拉鲁肽可减少 SAH 大鼠的早期脑损伤并减轻炎症反应和神经元凋亡。利拉鲁肽对 SAH 提供神经保护，这可能与抑制炎症和细胞凋亡有关。我们的研究结果表明，利拉鲁肽可减少 SAH 大鼠的早期脑损伤并减轻炎症反应和神经元凋亡。利拉鲁肽对 SAH 提供神经保护，这可能与抑制炎症和细胞凋亡有关。我们的研究结果表明，利拉鲁肽可减少 SAH 大鼠的早期脑损伤并减轻炎症反应和神经元凋亡。利拉鲁肽对 SAH 提供神经保护，这可能与抑制炎症和细胞凋亡有关。