鞘内注射PKCγ抑制剂GF109203X对骨癌痛大鼠痛觉过敏的影响  

Effect of intrathecal injection of PKCγ inhibitor GF109203X on hyperalgesia in rats with bone cancer pain

作　　者：肖兴鹏[1] 曹菲[1] 杨少兵[1] 高峰[1] 田学愎[1] 田玉科[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉科教研室,湖北武汉430030

出　　处：《第四军医大学学报》2008年第24期2214-2217,共4页Journal of the Fourth Military Medical University

基　　金：高等学校博士学科点专项科研基金(20060487048);国家自然科学基金(30672027)

摘　　要：目的:观察鞘内注射PKCγ抑制剂GF109203X对骨癌痛大鼠痛觉过敏的影响,探讨PKCγ在骨癌痛发病机制中的作用.方法:选取成年雌性Wistar大鼠30只(每组6只),随机分为5组,对照组(Naive组):随机选取6只正常大鼠且不做任何手术;骨癌痛(CIBP组):构建CIBP模型后,鞘内不注入任何药物;CIBP+生理盐水组(NS组):鞘内注入生理盐水10μL;CIBP+二甲基亚砜(DMSO)组(DMSO组):鞘内注入DMSO10μL;CIBP+GF109203X(GF109203X组):鞘内注入PKCγ抑制剂GF109203X10μL.观察各组大鼠注药前及鞘内注药后15,30,45,60,75min时的疼痛行为学变化,且各组大鼠分别在疼痛观察结束时灌注取材,冰冻切片后检测脊髓背角PKCγ的表达.结果:GF109203X组大鼠鞘内注射GF109203X后其各时点机械缩爪阈值较CIBP组明显升高(P<0.05),在注药后60min时其机械缩爪阈与正常组相接近,差异无统计学意义(P>0.05).DMSO组大鼠在注射DM-SO后其机械缩爪阈值也逐渐升高,在注药后45,60,75min时其阈值与CIBP组相比显著升高(P<0.05),但与GF109203X组相比,其升高后的各时点缩爪阈值仍分别小于GF109203X组相同时点缩爪阈值,且差异有统计学意义(P<0.05).经鞘内给药的NS组、DMSO组、GF109203X组,其大鼠脊髓背角PKCγ的表达量仍与CIBP组相接近,差异无统计学意义(P>0.05).结论:CIBP促使PKCγ表达增高且PKCγ参与了CIBP的发生和/或持续.AIM： To investigate the effect of intrathecal injec- tion with PKCγ inhibitor GF109203X on the hyperalgesia in rats with bone cancer pain. METHODS： Thirty female Wistar rats were randomly divided into 5 groups as follows （ n = 6 each） ： Naive group （normal rats and not received any intervention ）; CIBP group （unilateral intra-tibial injection with 4 × 10^4 Walker 256 carcinoma cells in 10 μL）; CIBP ＋ normal saline （NS group, intrathecal injection of normal saline 10 μL） ; CIBP ＋ DMSO group （DMSO group, intrathecal injection of DMSO 10 μL）; CIBP ＋ GF109203X （GF109203X group, intrathecal injection of GF109203X 10 μL）. Changes of pain behavior were assessed by mechanical withdrawal threshold （MWT） before injection as well as 15, 30, 45, 60, 75 min after injection. After pain threshold assessment was finished, the rats were sacrificed by perfusion with 4% paraform. The lumbar 4 - 6 spinal cord was removed and sectioned on a freezing microtome, and then detected for the expression of PKCγ through immunohistochemistry by image analysis method. RESULTS： After intrathecal administration of GF109203X, the MWT of GF109203X group was significantly higher than that of CIBP group （ P 〈 0.05 ）, and at 60 min post adminitration the MWT of GF109203X group was closed to the MWT of naive group （ P 〉 0.05 ）. Meanwhile, the MWT of DMSO group at 45, 60, 75 min post administration was significantly higher than that of CIBP group （P 〈 0.05）, but there were significant differences of the MWT between DMSO group and GF109203X group at the same time-point （P 〈 0.05）. However, the expression levels of PKCγ failed to display significant changes within spinal dorsal horn in the intrathecal injection groups, including NS group, DMSO group and GF109203X group as compared with that in CIBP group （ P 〉0. 05 ） by immunohistochemistry. CONCLUSION： PKCγ contributes to the development and/or maintenance of mechanical hyperalgesia produced by bone cancer pain.

关 键 词：骨肿瘤 疼痛 蛋白激酶C抑制剂 脊髓背角 注射 脊髓 

分 类 号：R33[医药卫生—人体生理学]