鞘内注射IGFBP-3慢病毒载体缓解大鼠骨癌痛的实验研究

Intrathecal injection of IGFBP-3 lentiviral vector attenuates bone cancer pain in rats

目的:探讨鞘内注射类胰岛素生长因子结合蛋白-3(insulin-like growth factor binding protein 3,IGFBP-3)过表达慢病毒对骨癌痛大鼠痛敏阈值的影响。方法:选用36只健康雌性SD大鼠,随机分为骨癌痛组、假手术组、IGFBP3慢病毒载体治疗组、空载慢病毒对照组。于左侧胫骨上端骨髓腔内注射Walker256乳腺癌细胞悬液10μL(2×107细胞),建立大鼠骨癌痛模型,IGFBP3慢病毒载体治疗组鞘内注射IGFBP-3过表达慢病毒。采用von Frey测痛仪在注射后不同时间点测定大鼠机械痛阈值。结果:骨癌痛组接种癌细胞后7天机械性痛敏阈值逐渐下降,接种后10天、14天、21天与假手术组比较,差异有统计学意义(P<0.05)。鞘内IGFBP3慢病毒后,IGFBP3慢病毒治疗组大鼠机械性痛敏阈值升高,14天和21天分别为9.8±1.6 g和7.68±1.1 g,高于空载慢病毒组的4.8±2.3 g和3.9±0.98 g,差异均具有统计学意义(P<0.05)。结论:IGFBP3可能参与骨癌大鼠痛敏反应,过表达IGFBP3可以缓解骨癌大鼠疼痛反应。

Objective:To clarify the expression of insulin like growth factor binding protein 3(IGFBP-3) for bone cancer pain in rats in DRG. Methods:Thirty-six normal female Sprague-Dawley rats weighing 160~210g were selected and rat models of bone cancer pain on the left side of the proximal tibia were established. The rat model of bone cancer pain was induced by injection of breast cancer cells (Walker 256) 10 μL (2×107 cell) into the left proximal tibia bone marrow cavity. At different time points after inoculation, Paw withdraw threshold of the left hind leg (operated side) was measured by von Frey fiber. Results: The mechanical pain threshold of bone cancer pain group decreased gradually 7 days after inoculation of cancer cells, and the difference was statistically significant compared with that of the sham operation group 10 days,14 days and 21 days after inoculation(P<0.05). After intrathecal injection of IGFBP-3 lentivirus, the mechanical pain sensitivity threshold of the rats treated with IGFBP-3 lentivirus increased, respectively 9.8±1.6 g and 7.68±1.1 g on 14 days and 21 days, higher than 4.8±2.3 g and 3.9±0.98 g in the noload lentivirus group, and the difference was statistically significant(P<0.05). Conclusion:IGFBP-3 in the DRGs may be involved in bone cancer pain sensitivity in rats,and overexpression of IGFBP-3 can reduce the bone cancer pain response in rats.