Lu Kwok-Tung, Wu Chang-Yen, Cheng Nai-Chi, Wo Yu-Yuan Peter, Yang Jen-Tsung, Yen Hao-Han, Yang Yi-Ling
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Eur J Pharmacol. 2006 Oct 24;548(1-3):99-105. doi: 10.1016/j.ejphar.2006.07.048. Epub 2006 Aug 4.
The present study was aimed to elucidate the possible role of Na+ -K+ -2Cl- -cotransporter (NKCC1) on traumatic brain injury-induced brain edema, cerebral contusion and neuronal death by using traumatic brain injury animal model. Contusion volume was verified by 2,3,5,-triphenyltetrazolium chloride monohydrate staining. NKCC1 mRNA expression was detected by RT-PCR and the protein expression of NKCC1 was measured by Western blot. We found that the expression of NKCC1 RNA and protein were up-regulated in choroid plexus apical membrane from 2 h after traumatic brain injury, peaked at 8 h, and lasted for 24 h. Rats in the experimental group displayed severe brain edema (water content: 81.45 +/- 0.32% compared with 78.38 +/- 0.62% of sham group) and contusion volume significantly increased 8 h after traumatic brain injury (864.14 +/- 28.07 mm3). Administration of the NKCC1 inhibitor bumetanide (15 mg/kg, I.V.) significantly attenuated the contusion volume (464.03 +/- 23.62 mm3) and brain edema (water content: 79.12 +/- 0.28%) after traumatic brain injury. Our study demonstrates that NKCC1 contributes to traumatic brain injury-induced brain edema and neuronal damage.
本研究旨在通过使用创伤性脑损伤动物模型，阐明钠钾氯共转运体1（NKCC1）在创伤性脑损伤诱导的脑水肿、脑挫伤和神经元死亡中可能发挥的作用。通过使用一水合三苯基四氮唑氯化物染色来验证挫伤体积。通过逆转录聚合酶链反应（RT-PCR）检测NKCC1 mRNA表达，并通过蛋白质印迹法测量NKCC1的蛋白质表达。我们发现，创伤性脑损伤后2小时起，脉络丛顶膜中NKCC1 RNA和蛋白质的表达上调，在8小时达到峰值，并持续24小时。实验组大鼠出现严重脑水肿（含水量：81.45±0.32%，而假手术组为78.38±0.62%），创伤性脑损伤后8小时挫伤体积显著增加（864.14±28.07立方毫米）。给予NKCC1抑制剂布美他尼（15毫克/千克，静脉注射）可显著减轻创伤性脑损伤后的挫伤体积（464.03±23.62立方毫米）和脑水肿（含水量：79.12±0.28%）。我们的研究表明，NKCC1促成创伤性脑损伤诱导的脑水肿和神经元损伤。
