吗啡对小鼠骨癌痛模型破骨细胞相关因子RANKL表达的影响

EFFECT OF MORPHINE ON THE EXPRESSION OF OSTEOCLAST ASSOCIATED CYTOKINE RANKL IN A MOUSE MODEL OF BONE CANCER

目的:建立小鼠骨癌痛模型,并给予吗啡处理,观察破骨细胞相关因子RANKL的表达,探讨痛觉过敏产生的机制。方法:建立雄性小鼠股骨癌痛模型,自造模后第1天起每天测量机械痛敏阈值,在第7天分别按每天给予吗啡20,10,3和1mg/kg将模型随机分为癌痛Ⅰ,Ⅱ,Ⅲ和Ⅳ四组(n=8)。利用RT-PCR和免疫组化法分别检测RANKL mRNA的表达和RANKL蛋白的表达。结果:第7天癌痛各组与对照组相比疼痛阈值有显著降低(P<0.05),应用吗啡后前4天疼痛阈值与对照组无差异,后3天癌痛Ⅰ组与对照组相比疼痛阈值降低有显著差异(P<0.05);癌痛各组随吗啡剂量增加RANKL表达增加,癌痛Ⅰ、Ⅱ组与对照组相比有显著性(P<0.05)。结论:RANKL可能与痛觉过敏的产生有关系。

Objective ： To establish a model of bone cancer pain with mouse and treat them with morphine to evaluate the mechanism of hyperalgesia by observing the expression of RANKL. Methods ： Model of femur bone cancer pain was made with male mice. Pain threshold of mechanical hyperalgesia was measured since the first day after the model being made. Morphine was administrated with dose of 20,10, 3st and1 mg/kg/day, respectively and divided into Ⅰ, Ⅱ, Ⅲ, Ⅳfour groups （ n = 8 ） randomly at the seventh day. Results ： Pain threshold of cancer pain group declined compared with the control group （ P 〈 0.05 ）. However, there was no significant difference of the pain threshold between cancer pain group and control group at the previous four days after treatment with morphine. But pain threshold of cancer pain Ⅰ group was significantly declined compared with the control group in the last three days （P 〈 0.05 ）. RANKL expression increased with the morphine dose increaed in cancer pain groups and expression increased significantly in cancer pain group Ⅰ , Ⅱcampared with the control group. Conclusion：RANKL may play a important role in the process of hyperalgesia.