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  

K252a relieved the persistent and postoperative pain through downregulating K＋-Cl- cotransporter 2 in the dorsal horn ofspinal cord in rats

作　　者：代淑红 孙玉娥[1] 荣辉[1] 马正良[1] 顾小萍[1] 

机构地区：[1]南京大学医学院附属鼓楼医院麻醉科,210008

出　　处：《国际麻醉学与复苏杂志》2016年第5期426-430,共5页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金（81171048,81471129）

摘　　要：目的 察鞘内注射酪氨酸激酶受体B（tyrosinekinasereceptorB，TrkB）抑制剂K252a对皮肤／肌肉切口牵拉术（skin／muscleincisionandretraction，SMIR）诱发的术后持续性痛大鼠脊髓背角钾氯共转运体-2（K＋-CI—cotransporter2，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＋-甲基亚砜（dimethylsulfoxide，DMSO）组和SMIR＋K252a组，每组13只。于术前1d及术后3、7、12、22、32d测定大鼠机械缩足反射阈值（mechanicalwithdrawalthreshold，MWT），Westernblot测定术后7d大鼠脊髓背角KCC2蛋白的表达。结果与对照组比较，术后7、12、22d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、22d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7d时SMIR组和sMIR＋DMS0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。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 aduh 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 [（22.5：1：2.3）, （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 inthe modulation of persistent postoperative pain evoked by SMIR in rats.

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 钾氯共转运体-2 

分 类 号：R614[医药卫生—麻醉学]