鞘内注射p38MAPK抑制剂对骨癌痛大鼠的抗伤害效应

THE ROLE OF P38 MITOGEN-ACTIVATED PROTEIN KINASE IN RATS WITH BONE CANCER PAIN

目的：探讨p38丝裂原活化蛋白激酶（p38MAPK）信号转导通路在大鼠骨癌痛中的作用。方法：雌性SD大鼠32只,体重150~170g,随机分为4组（n=8）：生理盐水对照组（NS组）、骨癌痛组（BC组）、二甲基亚砜组（DMSO组）和p38MAPK抑制剂组（SB203580组）。骨髓腔内注射Walk-er256细胞悬液制备大鼠骨癌痛模型,注射后10d DMSO组和SB203580组分别鞘内注射5%二甲基亚砜、SB203580（10μg）10μl,各组随机取8只大鼠,于注射前、注射后1、3、5、7、10d,鞘内给药后1、3、6、12、24h时采用von Frey丝测定术侧后爪机械缩足反射阈值（MWT）,用负重仪测大鼠双后肢负重差值。结果：骨髓腔内注射Walker256细胞悬液后7天大鼠术侧后爪MWT开始降低,双后肢负重差值开始增大;鞘内注射SB203580提高了MWT,减小了双后肢负重差值。结论：鞘内注射SB203580可减轻骨癌痛引起的痛敏,p38MAPK信号转导通路在骨癌痛中起重要作用。

Objective： To investigate the role of p38 mitogen-activated protein kinase（p38MAPK） in rats of bone cancer pain.Methods： 32 female SD rats weighing 150～170g were randomly divided into four groups（n=8 each）： NS group;bone cancer pain group;DMSO group and SB203580 group.Bone cancer pain was induced by injecting 5μl of Walker 256 mammary gland cancer cell suspension（107 cells/ml） into the bone marrow of left tibia in the later 3 groups.5% DMSO 10μl and SB203580 10μg in 10μl were intrathecally injected in the 3rd and 4rd group,respectively 10 days after establishing model of bone cancer pain.Paw withdrawal threshold to von Frey filament stimulation and the difference of weight bearing between hind paws were measured before and at 1,3,5,7,10d after bone cancer pain model was established and at 1,3,6,12,24h after IT DMSO or SB203580 injection.Results： The rats developed hyperalgesia at 7d after bone cancer pain had been induced.IT SB203580 significantly increased mechanical pain threshold.Conclusions： Intrathecal SB203580 can relieve the hyperalgesia induced by bone cancer pain.p38 MAPK signal pathway plays an important role in mdiating bone cancer pain.