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目的 探讨鞘内注射钙/钙调蛋白依赖性蛋白激酶Ⅱ( CaMKII)抑制剂KN93对骨癌痛小鼠脊髓NR2B蛋白表达的影响及机制.方法 SPF级雄性C3 H/HeJ小鼠36只,采用随机数字表法分为3组:假手术组(S组n=8)、骨癌痛组(BP组n=8)和KN93组(K组n=20).BP组和K组采用股骨远端骨髓腔注射20μl含NCTC 2472纤维肉瘤细胞的α-MEM的方法制备骨癌痛模型,S组骨髓腔注入不含NCTC 2472细胞的同体积α-MEM.K组于接种肿瘤细胞后14d鞘内注射溶于20％ DMSO的KN93 60 nmol/5μl,BP组和S组鞘内注射20％ DMSO 5μl.分别于肿瘤细胞接种前1d、鞘内注射KN93或溶媒前1 h、注射后1,2,4,24h(T0～5)时各组随机取8只小鼠,采用von Frev丝测定机械痛阈,并于各时点随机取3只小鼠处死取脊髓L3～5节段,采用Western blot法测定NR2B蛋白的表达.结果 与S组[机械痛阈(1.78 ±0.31)g、NR2B(0.33 ±0.04)]相比,除K组T3时机械痛阈差异无统计学意义(P＞0.05)外,BP组[(0.50±0.11)g]和K组[ (0.52 ±0.10)g]机械痛阈均降低(P＜0.05),BP组(1.78±0 34)和K组T2～5[分别为(1.11±0.14)、(0.73±0.03)、(1.11±0 15)、(1.89±0.32)]脊髓组织NR2B蛋白表达均上调(P＜0.05)；与BP组相比,K组T2～4机械痛阈升高,NR2B蛋白表达下调；与给药前T1相比,除K组T2～4机械痛阈升高外,各组各时点该指标差异均无统计学意义(P＞0.05).结论 鞘内注射KN93缓解小鼠骨癌痛的同时降低小鼠脊髓NR2B蛋白表达,CaMKII-NR2B信号通路可能参与了骨癌痛的形成.“,”Objective To investigate the effect of KN93,a CaMKII inhibitor,on the spinal NR2B expression in the bone cancer pain mouse and its underlying mechanism.Methods Thirty-six male C3IL/IIeJ mice were randomly divided into 3 groups:sham group( S,n =8 ),bone cancer pain group( BP,n =8 ) and KN93 group ( K,n=20).The mouse model of bone cancer pain was established by intra-femur inoculation of osteolytie NCTC 2472 cells in BP and K groups.At 14d post operation,mice in K group received intrathecal injection of 60nmol KN93/5μl in 20％ DMSO and mice in BP group and S group received 20％ DMSD 5μl respectively.Eight mice were selected randomly from each group at (1)d before inoculation,at 1 h before administration and at 1,2,4,24h after administration( T0-5 ) to be measured the paw withdrawal threshold(PWT) stimulated by von Frey filaments.Another 3 mice were sacrificed at the corresponding time point and the spinal cord L3 -5 were obtained for determination of NR2B expression by western blot.Results PWT was significantly decreased in group BP( (0.50 ± 0.11 ) g) and K( (0.52 ±0.10)g),except for group K at T3(P＞0.05),and NR2B cxpression up-regulated at T2-5 in BP( 1.78± 0.34),K groups ( ( 1.11 ± 0.14),(0.73 ± 0.03 ),( 1.11 ± 0.15 ),( 1.89 ± 0.32 ) ) compared with S group ( ( 1.78 ± 0.31 ) g,(0.33 ± 0.04),P ＜ 0.05 ).Compared with group BP,PWT was increased and NR2B expression down-regulated at T2-4 in group K.In contrast to T1,PWT at T2-4 upgraded in group K(P＜0.05 ),but no significant difference was observed in other groups (P＞ 0.05 ).Conclusion Intrathecal injection of KN93 can attenuate bone cancer pain in mice through inhibiting NR2B with a time-dependent manner and spinal CaMKII-NR2B pathway may participate in the development of bone cancer pain.