磷酸化钙/钙调素依赖性蛋白激酶Ⅱ在胫骨癌痛大鼠脊髓背角中的表达变化

Expression Changes of pCaMKⅡin Spinal Dorsal Horn in a Rat Model of Bone Cancer Pain

目的观察胫骨癌痛模型大鼠脊髓背角磷酸化钙/钙调素依赖性蛋白激酶Ⅱ(pCaMKⅡ)的表达变化,探讨CaMKⅡ在骨癌痛中的作用。方法选择雌性SD大鼠54只,随机分为3组(n=18):空白组(N),不作任何处理;对照组(C),左侧胫骨上段骨髓腔注入5μlHank’s液;模型组(M),左侧胫骨上段骨髓腔注入5μlWalker256细胞(2×107/ml)。分别于建模前及建模后6d、12d、18d测定大鼠机械缩足反射阈值和双后肢负重差值(n=6),并在相应时间点随机取6只大鼠脊髓L4～5段,采用免疫组织化学法检测pCaMKⅡ的表达。结果与N组、C组比较,建模后6～18dM组大鼠出现进行性加重的疼痛行为学改变,脊髓背角pCaMKⅡ表达逐渐升高(P<0.05)。结论脊髓pCaMKⅡ表达上调可能参与了大鼠骨癌痛的产生和维持。

Objective To observe the changes of pCaMKⅡexpression in the spinal dorsal horn in a rat model of bone cancer pain.Methods Fifty-four rats were randomly divided into three groups （n= 18）：the normol group,without any operation;the control group,injecting Hank’s 5μl into tibia medullary cavity;the model group,injecting Walker256 cells （2×107/ml）5 μl into tibia medullary cavity.Response of the injuried hind paw to mechanical stimulation with von Frey filament and the difference of weight bearing between both hind paws were measured before and 6 d、12 d and 18 d after establishing model.Then 6 rats in each group were killed 6 d、12 d and 18 d after establishing model separately and lumbar 4-5 spinal cord was removed for detection of pCaMKⅡby immunohistochemical study.Results Compared with the normal and contnol group,model group displayed gradul develepment of pain behaviors during 6-18 days after establishing model：And the expression of pCaMK-Ⅱ in spinal dorsal horn was up-regulated progressively.An up-regulated expression of pCaMKⅡ in spinal dorsal horn suggesting pCaMKⅡ may contribute to bone cancer pain.Conclusion Bone cancer pain results in an up-regulation in the expression of pCaMKⅡ in spinal dorsal horn,suggesting pCaMKⅡ may contribute to bone cancer pain.