中文摘要：

目的评价脊髓小胶质细胞CC趋化因子受体2（CCR2）在大鼠骨癌痛维持中的作用。方法健康雌性未交配sD大鼠50只，2月龄，体重160-180g，采用随机数字表法，将其分为5组（n=10）：假手术组（I组）、假手术＋RSl02895（CCR2拮抗剂）组（Ⅱ组）、骨癌痛组（Ⅲ组）、骨癌痛＋DMSO组（Ⅳ组）、骨癌痛＋RSl02895组（V组）。左侧胫骨干骺端骨髓腔内接种Walker256乳腺癌细胞制备大鼠骨癌痛模型。手术后10．12d，1I组和V组分别鞘内注射3μg/RSl02895 10μl，IV组鞘内注射DMSO 10μl，I组和Ⅲ组鞘内注射生理盐水10μl，1次／d。手术前1d、术后3、6、9、10、11、12d时测定机械痛阈，术后12d痛阈测定后，取L4-6脊髓组织，采用免疫组织化学法测定脊髓背角小胶质细胞激活标记物（OX-42）水平，采用ELISA法测定脊髓IL-lβ、IL-6及TNF-α的含量。结果与I组比较，Ⅲ组、Ⅳ组、V组术后6-12d时机械痛阈降低，OX-42阳性细胞数、脊髓IL-lβ、IL-6及TNF-a含量升高（P〈0．01），Ⅱ组上述指标差异无统计学意义（P〉0．05）；与Ⅲ组比较，V组术后10-12d时机械痛阈升高，OX-42阳性细胞数、脊髓IL-lβ、IL-6及TNF-a含量降低（P〈0．01），Ⅳ组上述指标差异无统计学意义（P〉0．05）。结论脊髓小胶质细胞CCR2参与大鼠骨癌痛的维持，其机制可能与激活小胶质细胞从而促进炎性细胞因子释放有关。

英文摘要：

Objective To evaluate the role of spinal microglial C-C chemokine receptor type 2 （CCR2） in the maintenance of bone cancer pain （BCP） in rats. Methods Fifty unmated female Sprague-Dawley rats, aged 2 months, weighing 160-180 g, were randomly divided into 5 groups （n = 10 each）： sham operation group （group I ）, sham operation ＋ RS102895 （CCR2 antagonist） group （group II ）, BCP group （group m ）, BCP ＋ dimethyl sulfoxide （ DMSO ） group （ group IV ）, and BCP ＋ RS102895 group （ group V ）. The rats were anesthetized with intraperitoneal chloral hydrate. BCP was induced by intra-tibial inoculation of 1 × 10^5 Walker 256 mammary gland carcinoma cells into the medullary cavity of the left tibial metaphysis. On 10-12 days after operation, 3 μg/μl RSI02895 10 μl was injected intrathecally once a day in Ⅱ and V groups, 10% DMSO 10μl was injected intrathecally once a day in IV group, and normal saline 10 μlwas injected intrathecally once a day in I and m groups. Mechanical paw withdrawal threshold was measured at 1 day before operation and 3, 6, 9, 10, 11 and 12 days after operation. After measurement of pain threshold at day 12 after operation, the lumbar segments （ I4-6 ） of the spinal cord were removed for determination of the level of ox-42 （spinal microglial activation marker） （by immuno-histochemistry） and contents of ILl-β, IL-6 and TNF-α （by ELISA） .Results Compared with group I , mechanical paw withdrawal threshold was significantly decreased at 6-12 days after operation, the number of ox-42 positive cells and contents of ILI-β, IL-6 and TNF-α were increased in Ⅲ , Ⅳ and V groups, and no significant change was found in the parameters mentioned above in group Ⅱ . Compared with group Ⅲ , mechanical paw withdrawal threshold was significantly increased at 10-12 days after operation, the number of ox-42 positive cells and contents of ILI-β, IL-6 and TNF-α were decreased in group V , and no significant change was found in the parameters