CX3C趋化因子受体1对骨癌痛大鼠吗啡耐受时脊髓背角μ受体和辣椒素受体表达的影响  

Effects of CX3 CR1 on expression of μ-receptor and TRPV1 in spinal dorsal horn of morphine- tolerent rats with bone cancer pain

作　　者：张亚军[1] 杨承祥[1] 王汉兵[1] 张涛[1] 刘希江[2] 田玉科[2] 

机构地区：[1]528000佛山市,中山大学附属佛山市第一人民医院麻醉科 [2]华中科技大学同济医学院附属同济医院麻醉学教研室

出　　处：《中华麻醉学杂志》2012年第5期569-572,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价CX3C趋化因子受体1（CX3CR1）对骨癌痛大鼠吗啡耐受时脊髓背角μ受体和辣椒素受体（TRPVI）表达的影响。方法清洁级成年雌性SD大鼠，体重180～200g，月龄3月，经k。棘突间隙行鞘内置管，取鞘内置管成功的大鼠48只，采用随机数字表法，将大鼠随机分为4组（n=12）：对照组（A组）、鞘内注射生理盐水组（AM组）、鞘内注射IgG组（GM组）和鞘内注射CX3CR1中和抗体组（BM组）。A组仅手术暴露右侧胫骨上段；其余3组右侧胫骨上段骨髓腔注入Walker256乳腺癌细胞10μl（400个／μl）建立骨癌痛模型，术后第10天开始鞘内注射吗啡20μg／kg，2次／d，连续7d，建立骨癌痛一吗啡耐受模型，注射吗啡第8天分别经鞘内注射相应溶液10μl，1次／d，连续3d。分别于接种Walker256乳腺癌细胞前（T0）、接种后第3、6、9天、注射吗啡第3、7天、鞘内注射抗体第3天（T1～T6）时测定机械缩足阈值（MWT）和机械缩足持续时间（MWD），于T6时测定痛阈后处死大鼠，取脊髓L4-6节段组织，采用Westernblot法检测脊髓背角小胶质细胞CX3CR1蛋白的表达，采用免疫组化法检测神经元μ受体和TRPV1的表达。结果与A组比较，BM组T2,3,5时、AM组和GM组T2,3.5.6时MWT下降，MWD升高，L时CX3CR1蛋白和TRPV1表达上调，μ受体表达下调（P〈0．01）；与AM组和GM组比较，BM组T6时MWT上升，MWD降低，CX3CR1蛋白和TRPV1表达下调，肛受体表达上调（P〈0．01）。AM组和GM组上述指标差异无统计学意义（P〉0．05）。结论CX3CR1可通过下调大鼠脊髓背角μ受体和上调TRPV1参与骨癌痛大鼠吗啡耐受的形成。Objective To investigate the effects of intrathecal （IT） CX3 CR1 neutralizing antibody （anti- FKR） on morphine tolerance in rats with bone cancer pain （BCP） and the underlying mechanism. Methods Forty-eight adult female SD rats aged 3 months weighing 180-200 g were randomized into 4 groups （ n = 12 each） ： group Ⅰ sham operation （S） ; group n BCP ＋ normal saline （NS） ; group Ⅲ BCP ＋ IgG （IgG） and group IV BCP ＋ anti-FKR. Bone cancer pain （BCP） was induced by injecting Walker 256 cancer cells 10/11 （400 cells/μl） into the medullary cavity of right tibia in groups Ⅱ , Ⅲ and Ⅳ . Ten days later morphine 20μg/kg was administered IT twice a day for 7 consecutive days. Starting from the 8th day NS, IgG and anti-KFR 10μl was administered IT once a day for 3 consecutive days in groups Ⅱ ,Ⅲ and IV respectively. Paw withdrawal threshold to yon Frey filament stimulation （MWT） and paw withdrawal duration （MWD） were determined before （To, baseline） and at 3, 6, 9 day after intra-tibial cancer cell inoculation （T1,2,3 ）, on the 3rd and 7th day of IT morphine （T4,5） and on the 3rd day of IT NS/IgG/anti-KFR （T6） . The .animals were killed at T6 after last pain behavior assessment. The lumbar segment （ L4-6 ） of the spinal cord was removed for determination of the expression of CX3 CRI protein （by Western blot）, μ-opioid receptor and TRPV1 receptor （by immuno-histochemistry） in the dorsal horn of spinal cord. Results IT morphine significantly eased BCP at T4, but morphine analgesia was significantly reduced on the 7th day of IT morphine in the 3 groups indicating morphine tolerance which was significantly relieved by anti-KFR in group Ⅳ . IT anti-KFR significantly down-regulated CX3 CR1 protein and TRPV1 receptor expression and up-regulated μ-opioid receptor in group Ⅳ as compared with IT NS and IgG in groups Ⅱ and Ⅲ . Conclusion IT anti-KFR can relieve morphine tolerance in the rats with bone cancer pain by up-regulating μ-

关 键 词：趋化因子CX3CL1 骨肿瘤 疼痛 吗啡 药物耐受性 受体 阿片样 μ TRPV阳离子通道 

分 类 号：R738[医药卫生—肿瘤]