Emergency Center, The Affiliated Wuxi People's Hospital, Nanjing Medical University, Wuxi, 214023, China,
Cell Biochem Biophys. 2013 Nov;67(2):615-22. doi: 10.1007/s12013-013-9549-0.
The increased intracranial pressure caused by brain edema following traumatic brain injury (TBI) always leads to poor patient prognosis. Aquaporin-4 (AQP-4) plays an important role in edema formation and resolution, which may provide a novel therapeutic target for edema treatment. In this present study, we found that propofol treatment, within a short time, after TBI significantly reduced brain edema in a controlled cortical injury rat model and suppressed in vivo expression of AQP-4. The ameliorating effect of propofol was associated with attenuated expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, the regulatory effect of propofol on AQP-4 expression was investigated in cultured astrocytes. Results showed that propofol could block the stimulatory effect of IL-1β and TNF-α on AQP-4 expression in cultured astrocytes. We also found that both NFκB and p38/MAPK pathways were involved in IL-1β and TNF-α-induced AQP-4 expression and that propofol functions as a dual inhibitor of NFκB and p38/MAPK pathways. In conclusion, treatment with propofol, within a short time, after TBI attenuates cerebral edema and reduces the expression of AQP-4. Propofol modulates acute AQP-4 expression by attenuating IL-1β and TNF-α expression and inhibiting IL-1β and TNF-α induced AQP-4 expression.
脑水肿导致创伤性脑损伤（TBI）后颅内压升高，始终导致患者预后不良。水通道蛋白-4（AQP-4）在水肿形成和消退中起重要作用，这可能为水肿治疗提供新的治疗靶点。在本研究中，我们发现 TBI 后短时间内给予异丙酚治疗可显著减轻控制性皮质损伤大鼠模型中的脑水肿，并抑制体内 AQP-4 的表达。异丙酚的改善作用与白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的表达减弱有关。此外，还研究了异丙酚对培养的星形胶质细胞中 AQP-4 表达的调节作用。结果表明，异丙酚可阻断 IL-1β和 TNF-α对培养的星形胶质细胞中 AQP-4 表达的刺激作用。我们还发现，NFκB 和 p38/MAPK 通路均参与了 IL-1β和 TNF-α诱导的 AQP-4 表达，而异丙酚作为 NFκB 和 p38/MAPK 通路的双重抑制剂发挥作用。总之，TBI 后短时间内给予异丙酚治疗可减轻脑水肿并降低 AQP-4 的表达。异丙酚通过减弱 IL-1β和 TNF-α的表达以及抑制 IL-1β和 TNF-α诱导的 AQP-4 表达来调节急性 AQP-4 表达。
