Igarashi Hironaka, Tsujita Mika, Suzuki Yuji, Kwee Ingrid L, Nakada Tsutomu
Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan.
Neuroreport. 2013 Apr 17;24(6):324-8. doi: 10.1097/WNR.0b013e32835fc827.
The effects of the aquaporin-4 (AQP-4) inhibitor TGN-020 on regional cerebral blood flow (rCBF) was examined in wild-type (WT) and AQP-4 knockout (KO) mice in vivo. Although baseline absolute rCBF of WT and KO mice were equivalent (158.9 ± 17.7 and 155.5 ± 10.4 ml/100 g/min, respectively), TGN-020 produced a significant increase in rCBF compared with saline-treated WT mice (control), reaching a plateau 20 min after administration (118.45 ± 8.13%, P<0.01). TGN-020 showed no effect on KO mice, supporting the concept that the observed increase in rCBF in WT mice was AQP-4 dependent. Administration of acetazolamide (positive control) produced an even greater increase in rCBF in WT compared with TGN-020 and a similar response in KO mice as well, reaching a sustained plateau 5 min after administration (138.50 ± 9.75 and 138.52 ± 9.76%, respectively, P<0.01 compared with baseline or saline-treated control mice). The study demonstrated that AQP-4 plays a role in regulation of rCBF.
在野生型（WT）和水通道蛋白4（AQP - 4）基因敲除（KO）小鼠体内，研究了水通道蛋白4抑制剂TGN - 020对局部脑血流量（rCBF）的影响。虽然WT和KO小鼠的基线绝对rCBF相当（分别为158.9±17.7和155.5±10.4 ml/100 g/min），但与生理盐水处理的WT小鼠（对照）相比，TGN - 020使rCBF显著增加，给药后20分钟达到平台期（118.45±8.13%，P<0.01）。TGN - 020对KO小鼠无作用，这支持了WT小鼠中观察到的rCBF增加是AQP - 4依赖性的这一概念。与TGN - 020相比，乙酰唑胺（阳性对照）给药后使WT小鼠的rCBF增加得更多，且在KO小鼠中也有类似反应，给药后5分钟达到持续平台期（分别为138.50±9.75和138.52±9.76%，与基线或生理盐水处理的对照小鼠相比，P<0.01）。该研究表明AQP - 4在rCBF调节中起作用。
