Büyükafşar Kansu, Yalçin Ipek, Kurt A Hakan, Tiftik R Nalan, Sahan-Firat Seyhan, Aksu Fazilet
Department of Pharmacology, Medical Faculty, Mersin University, Campus Yenişehir 33169, Mersin, Turkey.
Eur J Pharmacol. 2006 Jul 10;541(1-2):49-52. doi: 10.1016/j.ejphar.2006.04.042. Epub 2006 May 20.
The possible antinociceptive effect of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632), was investigated in mice by using the hot-plate and abdominal constriction response (writhing) tests. In addition, the expression of Rho-kinase protein (ROCK-2) was studied in the mouse brain and spinal cord by Western blotting. Male balb/c mice (n=8, for each group) were used in the experiment. Hot-plate latency and the number of writhes were recorded in control and in Y-27632-treated (1-5 mg/kg, i.p.) groups. Y-27632 (1 mg/kg) did not affect hot-plate latency; however, it considerably diminished the number of writhes, from 89+/-12 in control to 30+/-6 in the mice treated with 1 mg/kg Y-27632 (P=0.001). At a higher dose (5 mg/kg), Y-27632 prolonged the hot-plate latency from 8.7+/-1.0 s to 14.4+/-1.7 s (P=0.005) and decreased the number of writhes from 80+/-8 to 24+/-7 (P=0.002). Western blot analysis revealed that mouse spinal cord and brain homogenates expressed ROCK-2 protein. These results indicate that Rho-kinase may be involved in nociception and that its inhibitors, such as Y-27632, may represent a new type of antinociceptive drug.
使用热板法和腹部收缩反应（扭体）试验，在小鼠中研究了Rho激酶抑制剂（+）-（R）-反式-4-（1-氨基乙基）-N-（4-吡啶基）环己烷甲酰胺二盐酸盐一水合物（Y-27632）可能的抗伤害感受作用。此外，通过蛋白质印迹法研究了小鼠脑和脊髓中Rho激酶蛋白（ROCK-2）的表达。实验使用雄性balb/c小鼠（每组n = 8）。记录对照组和Y-27632处理组（1-5mg/kg，腹腔注射）的热板潜伏期和扭体次数。Y-27632（1mg/kg）不影响热板潜伏期；然而，它显著减少了扭体次数，从对照组的89±12次减少到用1mg/kg Y-27632处理的小鼠的30±6次（P = 0.001）。在较高剂量（5mg/kg）时，Y-27632将热板潜伏期从8.7±1.0秒延长至14.4±1.7秒（P = 0.005），并将扭体次数从80±8次减少到24±7次（P = 0.002）。蛋白质印迹分析显示小鼠脊髓和脑匀浆表达ROCK-2蛋白。这些结果表明，Rho激酶可能参与伤害感受，其抑制剂如Y-27632可能代表一种新型的抗伤害感受药物。
