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AQP4-siRNA 通过改变 TBI 大鼠创伤后 AQP4 极性逆转来减轻外伤性脑水肿。

AQP4-siRNA alleviates traumatic brain edema by altering post-traumatic AQP4 polarity reversal in TBI rats.

机构信息

Department of Radiology, Chongqing The Seventh Peoplés Hospital, Chongqing, China.

Department of Radiology, Hainan Women and Children's Medical Center, No. 15, Long Kun Nan road, Haikou, Hainan 572500, China.

出版信息

J Clin Neurosci. 2020 Nov;81:113-119. doi: 10.1016/j.jocn.2020.09.015. Epub 2020 Oct 5.

DOI:10.1016/j.jocn.2020.09.015
PMID:33222898
Abstract

The spatial and temporal distribution of aquaporin-4 (AQP4) expression in rat brain following brain trauma and AQP4-siRNA treatment, as well as corresponding pathological changes, were studied to explore the mechanism underlying the effect of AQP4-siRNA treatment on traumatic brain injury (TBI). The rats in the sham operation group had normal structure, with AQP4 located in the perivascular end-foot membranes and astrocytic membranes in a polarized pattern. The accelerated polarity reversal was observed in the TBI group in 1-12 h after TBI. During this period, AQP4 abundance on the astrocytic membrane is gradually increased, while AQP4 abundance on the perivascular end-foot membrane declined rapidly. Twelve hours after TBI, AQP4 expression was depolarized, showing a shift from the perivascular end-foot membrane to the astrocytic membrane. Pathological observation showed that vasogenic edema occurred immediately after TBI, at which time the extracellular space was expanded, leading to severe intracellular edema. AQP4-siRNA reduced the polarity reversal index at the early stage of TBI recovery and reduced edema, demonstrating the potential benefit of reduced AQP4 expression during recovery from TBI.

摘要

研究创伤性脑损伤(TBI)后大鼠脑水通道蛋白-4(AQP4)表达的时空分布及 AQP4-siRNA 治疗的相应病理变化,探讨 AQP4-siRNA 治疗对 TBI 作用的机制。假手术组大鼠结构正常,AQP4 位于血管周足膜和星形胶质细胞膜上呈极化分布。TBI 后 1-12 h,TBI 组可见 AQP4 极性加速逆转,此时星形胶质细胞膜上 AQP4 含量逐渐增加,而血管周足膜上 AQP4 含量迅速下降。TBI 后 12 h,AQP4 表达去极化,从血管周足膜转移到星形胶质细胞膜。病理观察显示,TBI 后即刻发生血管源性水肿,此时细胞外空间扩张,导致严重的细胞内水肿。AQP4-siRNA 降低了 TBI 恢复早期的极性反转指数,减少了水肿,表明在 TBI 恢复过程中降低 AQP4 表达具有潜在益处。

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