国际麻醉学与复苏杂志   2016, Issue (5): 10-10
    
K252a通过下调脊髓背角钾氯共转运体-2的表达缓解大鼠术后持续性痛
代淑红, 孙玉娥, 荣辉, 顾小萍, 马正良1()
1.南京大学医学院附属鼓楼医院
K252a relieved the persistent and postoperative pain through downregulating K+-Cl- cotransporter 2 in the dorsal horn of spinal cord in rats
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摘要:

目的 观察鞘内注射酪氨酸激酶受体B(tyrosine kinase receptor B, TrkB)抑制剂K252a对皮肤/肌肉切口牵拉术(skin/muscle incision and retraction, SMIR)诱发的术后持续性痛大鼠脊髓背角钾氯共转运体-2(K+-Cl- cotransporter 2, KCC2)蛋白表达的影响。 方法 采用随机数字表法将52只成年雄性SD大鼠随机分成假手术组(对照组)、SMIR组、SMIR+二甲基亚砜(dimethyl sulfoxide, DMSO)组和SMIR+K252a组,每组13只。于术前1 d及术后3、7、12、22、32 d 测定大鼠机械缩足反射阈值(mechanical withdrawal threshold, MWT),Western blot测定术后7 d大鼠脊髓背角KCC2蛋白的表达。 结果 与对照组比较,术后7、12、22 d 时MWT在SMIR组[(22.5±2.3)、(24.9±1.4)、(29.5±2.4) g]和SMIR+DMSO组[(24.0±1.9)、(24.8±2.3)、(26.7±2.1) g]明显降低(P<0.05);与SMIR组比较,术后7、12、22 d时MWT在SMIR+K252a组[(31.6±1.7)、(36.1±2.0)、(38.1±2.1) g]明显上调(P<0.05)。与对照组比较,术后7 d时SMIR组和SMIR+DMSO组的脊髓背角KCC2表达明显下调(P<0.05),SMIR+K252a组未检测到明显变化(P>0.05)。与SMIR组比较,SMIR+K252a组的脊髓背角KCC2表达明显上调(P<0.05)。 结论 脊髓背角KCC2的表达变化可能参与了大鼠术后持续性痛的形成。

关键词: 皮肤/肌肉牵拉; 术后持续性痛; 脑源性神经营养因子; 酪氨酸激酶受体B; 钾氯
Abstract:

Objective To observe the effects of intrathecal injections of tyrosine kinase receptor B(TrkB) inhibitor K252a on K+-Cl- cotransporter 2(KCC2) expression in the skin/muscle incision and retraction(SMIR)-induced persistent postoperative pain in rats. Methods Fifty two adult male SD rats were randomly and equally divided into four groups, namely the sham group(control group), SMIR group, SMIR+dimethyl sulfoxide(DMSO) group and SMIR+K252a group. Mechanical withdrawal threshold(MWT) was measured at the preoperative day 1 and postoperative days 3, 7, 12, 22 and 32, and KCC2 expression in the spinal dorsal horn was detected at postoperative day 7 by western blot. Results Compared with sham group, the MWT decreased significantly at postoperative days 7, 12, 22 in SMIR group[(22.5±2.3), (24.9±1.4), (29.5±2.4) g] and SMIR+DMSO group[(24.0±1.9), (24.8±2.3), (26.7±2.1) g](P<0.05). While compared with SMIR group, the MWT increased obviously at postoperative days 7, 12, 22 in SMIR+K252a group[(31.6±1.7), (36.1±2.0), (38.1±2.1) g](P<0.05). In addition, at postoperative days 7, compared with sham group, the expression of KCC2 in the spinal dorsal horn decreased significantly in SMIR group and SMIR+DMSO group(P<0.05), and no statistical significance in SMIR+K252a group(P>0.05). Compared with SMIR group, KCC2 expression in the spinal dorsal horn in SMIR+K252a group upregulated significantly(P<0.05). Conclusions KCC2 variations in the spinal dorsal horn may participate in the modulation of persistent postoperative pain evoked by SMIR in rats.

Key words: Skin/muscle retraction; Persistent postoperative pain; Brain derived neurophic factor; Tyrosine kinase receptor B; K+-Cl- cotransporter 2