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目的探讨趋化因子Fractalkine在骨癌痛中的作用及其脊髓部位的作用机制。方法采用Walker 256肿瘤细胞,注射在胫骨内建立骨癌痛模型。雌性SD大鼠40只,随机分为5组(n=8),Ⅰ组为Hank’s液对照组,Ⅱ组为骨癌痛组,Ⅲ组为对照组+CX3CR1中和抗体,Ⅳ组为骨癌痛组+IgG;Ⅴ组为骨癌痛组+CX3CR1中和抗体。术后第10~12天,鞘内分别注射CX3CR1中和抗体或IgG,每天1次,剂量10μg/10μl。分别于术前及术后隔日开始测定大鼠机械性痛阈值。术后第12天鞘内注射抗体后6 h处死大鼠,测定脊髓小胶质细胞标志物(OX-42)的表达水平。结果术后第10~12天,与Ⅰ组比较,Ⅱ组、Ⅳ组机械性痛阈值显著下降,脊髓OX-42染色阳性细胞数(Num)及积分吸光度(IA)显著增加,差异均有高度统计学意义(均P<0.01),Ⅲ组上述指标的差异无统计学意义(P>0.05);与Ⅱ组、Ⅳ组比较,Ⅴ组机械性痛阈值显著增高,脊髓OX-42染色Num及IA显著减少,差异均有高度统计学意义(均P<0.01)。结论Fractalkine通过激活脊髓小胶质细胞参与了骨癌痛的形成。
Objective To investigate the role of the chemokine Fractalkine in pain of bone cancer and its mechanism of action at spinal site. Methods Walker 256 tumor cells were injected into the tibia to establish a bone cancer pain model. Forty female Sprague-Dawley rats were randomly divided into five groups (n = 8). Group Ⅰ was Hank’s solution, group Ⅱ was bone cancer pain group, group Ⅲ was control group + CX3CR1 neutralizing antibody, and group Ⅳ was bone cancer Pain group + IgG; group V was bone cancer pain group + CX3CR1 neutralizing antibody. On day 10 to day 12, CX3CR1 neutralizing antibodies or IgG were injected intrathecally, once a day, at a dose of 10μg / 10μl. The threshold of mechanical pain in rats was measured before operation and every other day after operation. Rats were sacrificed 6 hours after intrathecal injection of antibody on the 12th day after operation, and the expression of spinal cord microglial marker (OX-42) was measured. Results On the 10th to 12th day after operation, the thresholds of mechanical pain in group Ⅱ and Ⅳ decreased significantly compared with those in group Ⅰ, and the number of positive cells (Num) and integral absorbance (IA) of OX-42 staining in spinal cord increased significantly (P <0.01). There was no significant difference between the above indexes in group Ⅲ (P> 0.05). Compared with group Ⅱ and group Ⅳ, the threshold of mechanical pain in group V was significantly higher than that in group Ⅲ IA significantly decreased, the differences were highly statistically significant (all P <0.01). Conclusion Fractalkine is involved in the formation of bone cancer pain through the activation of spinal cord microglia.