米诺环素对骨癌痛-吗啡耐受大鼠脊髓CX3C趋化因子受体1mRNA表达的影响  

Effect of minocycline on spinal CX3 C chemokine receptor 1 mRNA expression in morphine-tolerant rats with bone cancer pain

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

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉学教研室,武汉市430030 [2]中山大学附属佛山市第一人民医院麻醉科

出　　处：《中华麻醉学杂志》2011年第3期313-317,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30872441）

摘　　要：目的探讨米诺环素对骨癌痛-吗啡耐受大鼠脊髓CX3C趋化因子受体1（CX3CR1）mRNA表达的影响。方法清洁级雌性SD大鼠，体重180～200g，月龄3月，经L3,4间隙行鞘内置管，取鞘内置管成功的大鼠60只，采用随机数字表法，将大鼠随机分为4组：正常对照组（C组，n=10）、米诺环素对照组（M组，n=10）、骨癌痛-吗啡耐受组（BM组，n=20）和米诺环素治疗组（BM＋M组，n=20）。C组不作任何处理；BM组和BM＋M组右侧胫骨上段骨髓腔注入Walker256细胞10μl（400个／μl）制备骨癌痛模型，术后第10天开始鞘内注射吗啡20μg／kg（100μl），2次／d，连续7d，制备骨癌痛．吗啡耐受模型，注射吗啡第8天分别经鞘内注射20μl生理盐水或米诺环素0．25mg／kg（20阻），1次／d，连续3d；M组不行手术，于BM组注射吗啡第8天时鞘内注射米诺环素0．25mg／kg，1次，d，连续3d。于术前、术后3、6．9d、鞘内注射吗啡4、7、10、12d（T0～7）时测定机械缩足阈值（MWT）和机械缩足持续时间（MWD）。C组和M组于B时，BM组和BM＋M组于T6，7时取L4-6脊髓节段，采用免疫组化法检测小胶质细胞标记物——OX-42表达，采用实时PCR法检测CX3 CR1 mRNA表达水平。结果与C组和M组比较，BM组L2,3,5-7时、BM＋M组T2,3,5时MWT降低，MWD延长，CX3 CR1 mRNA和OX-42表达上调（P〈0．01）。与BM组比较，BM＋M组L．7时MWT升高，MWD缩短，CX3CR1 mRNA和OX-42表达下调（P〈0．01）。C组和M组上述指标差异无统计学意义（P〉0．05）。结论米诺环素可抑制骨癌痛-吗啡耐受大鼠脊髓CX3 CR1 mRNA的表达，可能是其拮抗吗啡耐受的机制之一。Objective To investigate the effect of minocycline on spinal CX3 C chemokine receptor 1 （CX3 CRI ） mRNA expression in morphlne-tolerant rats with bone cancer pain. Methods Sixty female SD rats weighing 180-200 g in which intrathecal （IT） catheter was successfully placed at L3,4 interspace without complica- tions were randomly divided into 4 groups： control group （group C, n = 10）; minocycline group （group M, n = 10） ; bone cancer pain ＋ morphine tolerance group （group BM, n = 20） and bone cancer pain ＋ morphine toler- ance ＋ minocycline group （group BM ＋ M, n = 20）. Bone cancer pain was induced by injection of breast cancer cells （Walker256） 10 IA （400μl） into upper segment of bone marrow of right tibia. Morphine tolerance was induced by IT injection of morphine 20 μg/kg twice a day for 7 consecutive days starting from the 10th day after intratibia injection in BM and BM ＋ M groups. Minocycline 0.25 mg/kg was injected IT once a day for 3 consecutive days in group M and after the model of bone cancer pain and morphine tolerance was established in group BM ＋ M. Mechanical withdrawal threshold （MWT） and mechanical withdrawal duration （MWD） were determined before （To, baseline） and at 3, 6 and 9 days after operation （T1-3 ） and at 4, 7, 10 and 12 days after IT morphine injection was started （T4-7） . The animals were sacrificed at T6 and T7 respectively in BM and BM ＋ M groups and at T7 in C and M groups. The lumbar segment of the spinal cord （ L4-6 ） was removed for determination of CX3 CR1 mRNA （by RT-PCR） and OX-42 expression （by immuno-histochemistry） .Results There was no significant difference in MWT and MWD at all time points between group C and group M. MWT was significantly decreased while MWD prolonged in morphine tolerant rats with cancer pain in group BM as compared with C and M groups. The hyperalgesia was significantly attenuated by IT minocycline in group BM ＋ M. Spinal CX3 CRI mRNA and OX-42 expression was significantly

关 键 词：米诺环素 骨肿瘤 疼痛 药物耐受性 吗啡 脊髓 趋化因子 CX3C 受体 

分 类 号：R96[医药卫生—药理学]