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目的探讨脊髓γ-氨基丁酸(GABA)能去抑制对细胞外信号调节激酶1/2(ERK1/2)活性的影响及其与痛行为改变的关系。方法正常小鼠鞘内注射(ith)比扣扣灵碱(荷包牡丹碱,bicuculline)50 ng.g-1(5μl)模拟GABA能去抑制,左后足底sc给予弗氏完全佐剂制备炎性疼痛模型,小鼠ith给予GABAA受体激动剂地西泮0.5μg.g-1(5μl)或ERK1/2抑制剂PD-98059 0.25μg.g-1(5μl)后,测定ERK1/2活性和小鼠缩足阈值。结果与正常对照组的缩足阈值(1.24±0.07)g相比,正常小鼠ith给予比扣扣灵碱50 ng.g-1的缩足阈值显著降低〔(0.42±0.17)g,P<0.05〕,给予PD-98059 0.25μg.g-1后缩足阈值显著升高〔(1.29±0.37)g,P<0.05〕。与炎性疼痛模型组的缩足阈值(0.28±0.06)g相比,炎症小鼠ith给予地西泮0.5μg.g-1的缩足阈值显著升高〔(0.99±0.12)g,P<0.05〕,且给予PD-98059 0.25μg.g-1后缩足阈值也显著升高〔(0.97±0.17)g,P<0.05〕。Western免疫印迹结果显示,与正常对照组相比,比扣扣灵碱显著提高ERK2的磷酸化水平〔(152±24)%,P<0.05〕。并且弗氏完全佐剂也可提高小鼠脊髓ERK2的磷酸化水平〔(163±42)%,P<0.05〕,ith给予地西泮0.5μg.g-1,则显著降低CFA诱发的小鼠脊髓ERK2的磷酸化水平〔(91±34)%,P<0.05〕,同时地西泮和PD-98059有效缓解炎性疼痛症状。结论 GABA能去抑制对脊髓背角ERK2有激活作用,并与炎性疼痛的形成有关。
Objective To investigate the effect of γ-aminobutyric acid (GABA) on the activity of extracellular signal-regulated kinase 1/2 (ERK1 / 2) and its relationship with the change of pain behavior. Methods Normal mice were intrathecally injected with (ith) 50 ng.g-1 (5 μl) of bicuculline to inhibit GABA deprivation, and left dermal sc was given complete Freund’s adjuvant to prepare inflammation Pain model, ERK1 / 2 activity was measured after ith administration of 0.5 μg.g-1 (5 μl) of GABAA receptor agonist diazepam or 0.25 μg.g-1 of ERK1 / 2 inhibitor PD-98059 (5 μl) And mouse contraction foot threshold. Results Compared with the contractile threshold (1.24 ± 0.07) g in normal control group, the contractile threshold of 50 ng.g-1 of ithbugginase in normal mice was significantly lower 〔(0.42 ± 0.17) g, P < 0.05]. The contractile threshold of PD-98059 0.25μg.g-1 was significantly increased [(1.29 ± 0.37) g, P <0.05〕. Compared with the contractile threshold of inflammatory pain model group (0.28 ± 0.06) g, the contractile threshold of 0.5μg.g-1 of mpatherapy ith given diazepam significantly increased 〔(0.99 ± 0.12) g, P < 0.05〕, and PD-98059 0.25μg.g-1 reduced contractile threshold was also significantly increased 〔〕 (0.97 ± 0.17) g, P <0.05 〔〕〕. Western blot results showed that compared with the normal control group, the ratio of phosphorylation of ERK2 was significantly increased than that of the control group [(152 ± 24)%, P <0.05). Freund’s complete adjuvant also increased phosphorylation of ERK2 in the spinal cord of mice [(163 ± 42)%, P <0.05], while 0.5 μg.g-1 of diazepam significantly reduced CFA-induced mice The level of phosphorylation of ERK2 in the spinal cord [(91 ± 34)%, P <0.05〕, and diazepam and PD-98059 effectively relieved the inflammatory pain. Conclusion GABA can inhibit the activation of ERK2 in spinal dorsal horn and is related to the formation of inflammatory pain.