CAJ | 학술논문

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56只,体重150～170 g,随机分为4组(n=14):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Walker256细胞悬液制备大鼠骨癌痛模型,注射后10 d,DMSO组和SB203580组分别鞘内注射5%二甲基亚砜和SB203580(10 μg)10 μl.各组随机取8只大鼠,于注射Walker256细胞悬液前、注射后1、3、5、7、10 d,鞘内给药后1、3、6、12、24 h时采用von Frey纤维丝测定术侧后爪机械缩足反射阈值(MWT);各组余6只大鼠鞘内给药后6 h时取L_(4,5)脊髓,采用免疫组化法检测脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白(pCREB)的表达水平.结果骨髓腔内注射Walker256细胞悬液后7 d大鼠术侧后爪MWT开始降低,鞘内注射SB203580提高了MWT;骨髓腔内注射Walker256细胞悬液后脊髓背角pCREB表达上调,鞘内注射SB203580后脊髓背角pCREB表达下调.结论鞘内注射SB203580可通过抑制脊髓背角pCREB的表达减轻骨癌痛;p38MAPK信号转导通路在骨癌痛中起重要作用.
목적 탐토p38사렬원활화단백격매(p38MAPK)신호전도통로재대서골암통중적작용.방법 자성sD대서56지,체중150～170 g,수궤분위4조(n=14):생리염수대조조(NS조)、골암통조(BC조)、이갑기아풍조(DMSO조)화p38MAPK억제제조(SB203580조).골수강내주사Walker256세포현액제비대서골암통모형,주사후10 d,DMSO조화SB203580조분별초내주사5%이갑기아풍화SB203580(10 μg)10 μl.각조수궤취8지대서,우주사Walker256세포현액전、주사후1、3、5、7、10 d,초내급약후1、3、6、12、24 h시채용von Frey섬유사측정술측후조궤계축족반사역치(MWT);각조여6지대서초내급약후6 h시취L_(4,5)척수,채용면역조화법검측척수배각린산화배린산선감반응원건결합단백(pCREB)적표체수평.결과 골수강내주사Walker256세포현액후7 d대서술측후조MWT개시강저,초내주사SB203580제고료MWT;골수강내주사Walker256세포현액후척수배각pCREB표체상조,초내주사SB203580후척수배각pCREB표체하조.결론 초내주사SB203580가통과억제척수배각pCREB적표체감경골암통;p38MAPK신호전도통로재골암통중기중요작용.
Objective To investigate the role of p38 mitogen-activated protein kinase(p38MAPK) in bone cancer pain in rats.Methods Fifty-six female SD rats weighing 150-170 g were randomly divided into 4 groups (n= 14 each): group ⅠNS operation; group Ⅱ bone cancer pain; group Ⅲ DMSO and group Ⅳ SB203580. Bone cancer pain was induced by injecting Walker256 mammary gland cancer cell suspension (107 cells/ml) 5 μl into the bone marrow of left tibia in group Ⅱ,Ⅲ and Ⅳ.5% DMSO 10 μl and SB203580 10 μg in 10 μl were injected IT in group Ⅲ and Ⅳ respectively at 10 days after bone cancer pain model was established. Paw withdrawal threshold to von Frey filament stimulation was measured before and at 1,3,5,7,10 d after bone cancer pain model was established and at 1,3,6, 12,24 h after IT DMSO or SB203580 injection. Six animals in each group were killed at 6 h after IT DMSO and SB203580 injection. The L_(4,5) lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal born by immuno-histochemistry. Results The rats developed hyperalgesia at 7 d after bone cancer pain had been induced. IT SB203580 significantly increased mechanical pain threshold. The number of pCREB positive neurons in the dorsal horn of L_(4,5) segment of the spinal cord was significantly increased by bone cancer pain. IT SB203580 significantly attenuated the increase in pCREB expression induced by bone cancer pain. Conclusion Intrathecal SB203580 can relieve the hyperalgesia induced by bone cancer pain and inhibit CREB phosphorylation in the spinal dorsal horn. p38MAPK signal pathway plays an important role in bone cancer pain.