骨癌痛大鼠背根神经节酸感受离子通道3表达的变化

Changes in expression of acid-sensing ion channel 3 in dorsal root ganglion in a rat model of bone cancer pain

目的探讨骨癌痛大鼠背根神经节酸感受离子通道3（ASIC3）表达的变化。方法雌性SD大鼠24只，3～4周龄，体重180～220g，采用随机数字表法，将其随机分为2组：对照组（n=8）和骨癌痛组（n=16）。骨癌痛组于左侧胫骨骨髓腔内注射5μl Walker256肿瘤细胞制备骨癌痛模型，s组左侧胫骨骨髓腔内注射生理盐水5μl。分别于接种当天（T0）和接种后1、3、5、7、9、11、14d（T1-7）时，称量大鼠体重，测定机械痛阈。对照组于接种后14d时，骨癌痛组分别于接种后7和14d时，取大鼠左侧胫骨，行病理学检查和影像学检查，观察肿瘤细胞的生长和骨质破坏状况，采用免疫荧光法测定背根神经节ASIC3的表达。结果骨癌痛组接种后14d时发生病理学损伤，胫骨破坏明显，多处骨皮质缺失。与对照组比较，骨癌痛组L3-7，时体重降低，T4-7，时机械痛阈降低，接种后14d时ASIC3表达上调（P〈0．05）。结论大鼠骨癌痛的形成和维持可能与背根神经节ASIC3表达上调有关。

Objective To investigate the changes in the expression of acid-sensing ion channel 3 （ASIC3） in the dorsal root ganglion （DRG） in a rat model of bone cancer pain. Methods Twenty-four female SD rats, aged 3-4 yr, weighing 180-220 g, were randomly divided into 2 groups： sham operation group （group S, n = 8） and bone cancer pain group （group P, n = 16）. Bone cancer pain was induced by intra-tibial inoculation of 10/A Walker 256 cancer cell suspension in group P, while group S received intra-tibial inoculation of 5/11 normal saline. Body weight and paw withdrawal threshold to mechanical stimulation with yon Frey filaments （MWT） were measured at 0, 1, 3, 5, 7, 9, 11 and 14 d after cancer cell inoculation. The tibia was removed at 14 d after cancer cell inoculation in group S and at 7 and 14 d after cancer cell inoculation in group P for pathological and imaging examinations. The tumor cell growth and bony destruction were observed. The expression of ASIC3 in the DRG was determined by immunofluorescence. Results Pathological damage occurred at 14 d after cancer cell inoculation, bony destruction was observed obviously, and cortical bone was missing in many places. Compared with group S, body weight at T3-7 and MWT at T2-7 were significantly decreased, and the expression of ASIC3 was up-regulated at 14 d after cancer cell inoculation in group P （ P 〈 0.05 ）. Conclusion Up-regulation of the expression of ASIC3 in the DRG is involved in the development and maintenence of bone cancer pain in rats.