慢病毒介导的水通道蛋白 4 基因沉默对创伤性脑损伤大鼠模型的神经保护作用。
Neuroprotective effects of lentivirus-mediated aquaporin-4 gene silencing in rat model of traumatic brain injury.
机构信息
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Neursurgery, Dong Zhimen Hospital Beijing University of Chinese Medicine, Beijing, China.
出版信息
Neurol Res. 2022 Aug;44(8):692-699. doi: 10.1080/01616412.2022.2039509. Epub 2022 Feb 21.
BACKGROUND
Traumatic brain injury (TBI) is a common clinical condition caused by external force. Aquaporin-4 (AQP4) in astrocytes participates in the generation of cell swelling in TBI.
METHODS
This research explored the effect of AQP4 gene silencing in a TBI rat model. A hydraulic craniocerebral trauma instrument was employed for establishing the TBI rat model. AQP4 expression in the brain was inhibited by the injection of AQP4 shRNA-lentiviral vector. The expression of relative genes was evaluated by Western blot and qRT-PCR. Neuronal apoptosis was analyzed by TUNEL assay.
RESULTS
AQP4 shRNA treatment inhibited AQP4 expression in the brain of rats with TBI. AQP4 shRNA alleviated TBI-induced brain edema and neurological deficit in rats. Neuronal apoptosis and astrocyte activation in TBI rats were reduced by AQP4 silencing.
CONCLUSION
This research demonstrated that AQP4 shRNA-induced silencing of AQP4 in the TBI rat model reduced the expression of AQP4 and GFAP, alleviated brain edema, neurological deficit, neuronal apoptosis and inhibited astrocyte activation.
背景
创伤性脑损伤（TBI）是一种由外力引起的常见临床病症。星形胶质细胞中的水通道蛋白 4（AQP4）参与了 TBI 中的细胞肿胀产生。
方法
本研究探讨了 AQP4 基因沉默在 TBI 大鼠模型中的作用。采用液压颅脑损伤仪建立 TBI 大鼠模型。通过注射 AQP4 shRNA 慢病毒载体抑制脑内 AQP4 表达。通过 Western blot 和 qRT-PCR 评估相对基因的表达。通过 TUNEL 检测分析神经元凋亡。
结果
AQP4 shRNA 处理抑制了 TBI 大鼠脑内 AQP4 的表达。AQP4 shRNA 减轻了 TBI 诱导的大鼠脑水肿和神经功能缺损。AQP4 沉默减少了 TBI 大鼠的神经元凋亡和星形胶质细胞激活。
结论
本研究表明，AQP4 shRNA 诱导的 TBI 大鼠模型中 AQP4 的沉默降低了 AQP4 和 GFAP 的表达，减轻了脑水肿、神经功能缺损、神经元凋亡，并抑制了星形胶质细胞激活。
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