胫骨癌痛大鼠脊髓星形胶质细胞的活化

Activation of spinal astrocytes in a rat model of tibial cancer pain

目的观察胫骨癌痛大鼠脊髓星形胶质细胞的活化情况，探讨骨癌痛产生与维持的机制。方法Walker256乳腺癌细胞经大鼠体内腹水传代增殖，种植于大鼠左侧胫骨建立胫骨癌痛模型。雌性SD大鼠35只，体重150～180g，随机分为3组：对照组（C组，n=5）、热杀死肿瘤细胞组（K组，n=15）、胫骨癌痛组（P组，n=15）。C组选取5只大鼠，K组和P组于种植后第6天、第12天和第18天随机取5只大鼠测定左后足机械痛阈，随后处死大鼠，取左侧L4～6脊髓组织，采用免疫组化方法检测脊髓背角胶质原纤维酸性蛋白（GFAP）表达水平。结果与C组比较，K组大鼠左后足机械痛阈及左侧脊髓背角GFAP表达差异无统计学意义（P〉0．05）。与K组比较，P组于种植癌细胞后第6天、第12天及第18天时大鼠左后足机械痛阈降低，左侧脊髓背角GFAP表达升高（P〈0．01）。与种植癌细胞后第6天比较，种植癌细胞后第12、18天时P组大鼠左后足机械痛阈下降，左侧脊髓背角GFAP表达升高（P〈0．01），而P组种植癌细胞后第12天与第18天比较，大鼠左后足机械痛阈与脊髓背角GFAP表达差异无统计学意义（P〉0．05）。结论脊髓星形胶质细胞的活化与胫骨癌痛的产生与维持有关。

Objective To investigate the activation of spinal astrocytes in a rat model of tibial cancer pain. Methods Thirty-five female SD rats weighing 150-180 g were randomly divided into 3 groups： control group （C, n = 5）, heat-killed breast cancer cell group （K, n = 15） and tibial cancer pain group （P, n = 15）. Tibial cancer pain model was produced by inoculations of Walker 256 breast cancer cells in the left tibial medullary cavity of rats. Five rats were randomly selected in group C and on 6th, 12th and 18th day after inoculation in group K and P for detection of the mechanical threshold of the left hind paw, then the rats were killed and lelf L4-6 spinal cord tissues were removed for determination of the expression of glial fibrillary acidic protein （GFAP） by immunohistochemical method. Results There were no significant differences in the mechanical threshold and expression of GFAP in the left spinal cord dorsal horn between group C and K （ P 〉 0.05 ） . The mechanical threshold was significantly lower and the expression of GFAP in the left spinal cord dorsal horn higher on 6th, 12th and 18th day after inoculation in group P than in group K （P 〈 0.01 ）. As compared with those on 6th day after inoculation, the mechanical threshold was significantly lower and the expression of GFAP in the left spinal cord dorsal horn higher on 12th and 18th day after inoculation（P 〈 0.01）, but without significant differences between 12th and 18th day after inoculation in group P. Conclusion The activation of spinal astrocytes is involved in the induction and maintenance of tibial cancer pain in rats.