二甲双胍通过减少STAT3磷酸化缓解大鼠骨癌痛  

Metformin attenuates bone cancer pain by inhibiting expression of p-STAT3

作　　者：葛安琪[1,2] 殷红 李登峰[1,2] 张辉[1,2] 赵伟[1,2] 颜明[1,2] 苗蓓[1,4] 

机构地区：[1]徐州医科大学江苏省麻醉学重点实验室,江苏徐州221000 [2]徐州医科大学附属医院麻醉科,江苏徐州221000 [3]徐州医科大学第二附属医院肿瘤内科,江苏徐州221000 [4]徐州医科大学附属医院消化科,江苏徐州221000

出　　处：《中国药理学通报》2017年第6期844-848,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81200861)

摘　　要：目的探讨二甲双胍对骨癌痛大鼠的镇痛作用及其对脊髓背角中磷酸化信号转导子与转录激活子3(phospho-signal transducers and activators of transcription 3,p-STAT3)表达的影响。方法健康成年♀SD大鼠48只,体质量200~220 g,随机分为4组(n=12):假手术+生理盐水组(Sham+NS组)、假手术+二甲双胍组(Sham+Metformin组)、骨癌痛+生理盐水组(BCP+NS组)、骨癌痛+二甲双胍组(BCP+Metformin组)。BCP+NS组和BCP+Metformin组大鼠制备骨癌痛模型,Sham+NS组和Sham+Metformin组大鼠胫骨骨髓腔注入生理盐水对照。4组大鼠于术后d 7~14分别腹腔内注射生理盐水或二甲双胍200 mg·kg^(-1),1次/日。测定造模前1 d及造模后3、5、7、10、12、14 d机械缩足反射阈值(mechanical withdrawal threshold,MWT)。行为学测试完成后选择d 14大鼠,用免疫荧光和Western blot方法检测大鼠脊髓背角中p-STAT3的表达。结果腹腔注射二甲双胍明显逆转了骨癌痛大鼠机械痛敏;腹腔注射二甲双胍明显抑制了脊髓背角p-STAT3的表达。结论二甲双胍可以通过抑制骨癌痛大鼠脊髓背角p-STAT3的表达减轻骨癌痛大鼠的病理性疼痛。Aim To investigate the effects of metformin on phospho-signal transducers and activators of transcription 3( p-STAT3) expression in the spinal dorsal horn in rats with bone cancer pain( BCP). Methods Healthy female SD rats weighing 200 ~ 220 g were randomly divided into four groups( n = 12 each) : Sham +NS,Sham + Metformin,BCP + NS,BCP + Metformin groups. Normal saline or metformin( 200 mg · kg^(-1))was given intraperitoneally once a day at 7 ~ 14 day after surgery in four groups. Mechanical withdrawal threshold( MWT) was measured on-1,3,5,7,10,12,14 day after BCP. The L_(4-6) segments of spinalcords were used to detect the expression of p-STAT3 by Western blot and immunohistochemical staining technique after the behavioral test was completed on day14. Results Intraperitoneal injection of metformin reversed hyperalgesia and suppressed the expression of pSTAT3 in BCP rats. Conclusion Metformin can attenuate BCP by inhibiting the expression of p-STAT3 in the spinal dorsal horn.

关 键 词：骨肿瘤 疼痛 二甲双胍 信号转导子与转录激活子3 磷酸化 脊髓背角 大鼠 

分 类 号：R-332[医药卫生] R322.8