Xiong Yaozu, Wang Yifei, Li Mingyue, Yu Changhua, Tong Yusuo, Xu Xiaoting
Department of Radiotherapy for Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Pathology, Children's Hospital of Soochow University, Suzhou, China.
Front Pharmacol. 2025 May 8;16:1534729. doi: 10.3389/fphar.2025.1534729. eCollection 2025.
The expression changes of aquaporin-4 (AQP4) in radiation-induced brain jinjury (RIBI) and whether it is involved in the pathologic development of RIBI are currently unknown. In this study, we constructed a RIBI model by whole-brain radiation of Sprague-Dawley (SD) rats and tried to reveal the role of AQP4 in RIBI. The specific inhibitor AER-271 was used to inhibit the expression of AQP4 in RIBI to explore its neuro-protective effect.
SD rats were randomly divided into Sham group and IR group. The trend and role of AQP4 in RIBI were explored by H&E staining, Western blot, brain tissue water content measurement, Evans blue (EB) osmolality assay, and immunofluorescence staining. Then SD rats were randomly divided into Sham group, AER-271 group, IR group and IR+AER-271 group to investigate the neuroprotective effects of AER-271 by H&E staining, Western blot, brain tissue water content measurement, EB osmolality assay, immunofluorescence staining, qRT-PCR and Elisa.
Radiation promoted the expression of AQP4 in rat brain tissue, leading to its "depolarized" distribution. The expression level of AQP4 correlated with the severity of cerebral edema. Treatment with AER-271 reduced cerebral edema, attenuated inflammation and apoptosis, and maintained the integrity of the blood-brain barrier (BBB) in RIBI rats.
AQP4 is involved in regulating the subsequent inflammatory response, BBB injury and apoptosis by mediating the development of cerebral edema during the acute phase of RIBI. AER-271 is expected to be a promising therapeutic candidate for the treatment of RIBI by inhibiting the expression of AQP4.
水通道蛋白4（AQP4）在放射性脑损伤（RIBI）中的表达变化及其是否参与RIBI的病理发展目前尚不清楚。在本研究中，我们通过对Sprague-Dawley（SD）大鼠进行全脑照射构建了RIBI模型，并试图揭示AQP4在RIBI中的作用。使用特异性抑制剂AER-271抑制RIBI中AQP4的表达，以探索其神经保护作用。
将SD大鼠随机分为假手术组和照射组。通过苏木精-伊红（H&E）染色、蛋白质免疫印迹法（Western blot）、脑组织含水量测定、伊文思蓝（EB）渗透压测定和免疫荧光染色，探讨AQP4在RIBI中的变化趋势和作用。然后将SD大鼠随机分为假手术组、AER-271组、照射组和照射+AER-271组，通过H&E染色、Western blot、脑组织含水量测定、EB渗透压测定、免疫荧光染色、实时荧光定量聚合酶链反应（qRT-PCR）和酶联免疫吸附测定（Elisa）研究AER-271的神经保护作用。
辐射促进大鼠脑组织中AQP4的表达，导致其“去极化”分布。AQP4的表达水平与脑水肿的严重程度相关。用AER-271治疗可减轻RIBI大鼠的脑水肿，减轻炎症和细胞凋亡，并维持血脑屏障（BBB）的完整性。
AQP4通过在RIBI急性期介导脑水肿的发展，参与调节随后的炎症反应、BBB损伤和细胞凋亡。AER-271有望通过抑制AQP4的表达成为治疗RIBI的有前景的治疗候选药物。
