CAJ | 학술논문

目的评价胫骨癌痛大鼠脊髓细胞外信号调节激酶5(ERK5)活性的变化.方法雌性未交配SD大鼠108只,体重160～ 180 9,采用随机数字表法,将其分为3组(n=36):对照组(C组)、假手术组(S组)和胫骨癌痛组(BCP组).BCP组胫骨骨髓腔内注射Walker256乳腺癌细胞混悬液制备大鼠胫骨癌痛模型；S组胫骨骨髓腔内注射等容量生理盐水；C组不作任何处理.于接种前1d、接种后3、5、7、14和21 d时,测定机械痛阈.C组和S组于接种后21 d痛阈测定结束后随机处死6只大鼠,BCP组分别于接种后3、5、7、14和21 d痛阈测定结束后随机处死6只大鼠,取脊髓组织,采用Westernblot法测定脊髓背角磷酸化ERK5(p-ERK5)、ERK5和Fos蛋白的表达.结果 C组和S组各时点机械痛阈、脊髓背角p-ERK5、ERK5和Fos蛋白的表达差异无统计学意义(P＞0.05).与C组和S组比较,BCP组接种后7-21 d时机械痛阈下降,接种后5-21 d时脊髓p-ERK5和Fos蛋白表达上调(P＜0.05),ERK5表达差异无统计学意义(P＞0.05).结论大鼠胫骨骨髓腔内注射肿瘤细胞可能通过增强脊髓ERK5活性,导致其下游Fos蛋白的释放,从而诱发骨癌痛.
목적 평개경골암통대서척수세포외신호조절격매5(ERK5)활성적변화.방법 자성미교배SD대서108지,체중160～ 180 9,채용수궤수자표법,장기분위3조(n=36):대조조(C조)、가수술조(S조)화경골암통조(BCP조).BCP조경골골수강내주사Walker256유선암세포혼현액제비대서경골암통모형；S조경골골수강내주사등용량생리염수；C조불작임하처리.우접충전1d、접충후3、5、7、14화21 d시,측정궤계통역.C조화S조우접충후21 d통역측정결속후수궤처사6지대서,BCP조분별우접충후3、5、7、14화21 d통역측정결속후수궤처사6지대서,취척수조직,채용Westernblot법측정척수배각린산화ERK5(p-ERK5)、ERK5화Fos단백적표체.결과 C조화S조각시점궤계통역、척수배각p-ERK5、ERK5화Fos단백적표체차이무통계학의의(P＞0.05).여C조화S조비교,BCP조접충후7-21 d시궤계통역하강,접충후5-21 d시척수p-ERK5화Fos단백표체상조(P＜0.05),ERK5표체차이무통계학의의(P＞0.05).결론 대서경골골수강내주사종류세포가능통과증강척수ERK5활성,도치기하유Fos단백적석방,종이유발골암통.
Objective To evaluate the changes in the activity of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord in a rat model of bone cancer pain (BCP).Methods One hundred and eight female Sprague-Dawley rats,weighing 160-180 g,were randomly divided into 3 groups (n =36 each):control group (group C):sham operation (group S) and group BCP.In group BCP Walker 256 mammary gland cancer cell suspension (1 × 105 cells/ml) 5 μl was injected into the left tibia,while in group S normal saline 5μl was injected into the left tibia instead of cancer cell suspension.Group C underwent no treatment.Mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) was measured at 1 day before inoculation and 3,5,7,14 and 21 days after inoculation.Six rats were sacrificed after the last measurement of MWT in groups C and S or after measurement of MWT at 3,5,7,14 and 21 days after inoculation in group BCP and the spinal cord was removed for determination of the expression of phosphorylated ERK5 (p-ERK5),ERK5 and Fos protein in the spinal dorsal horn by Western blot analysis.Results There was no significant difference in the MWT and expression of p-ERK5,ERK5 and Fos protein at each time point between groups C and S (P ＞ 0.05).Compared with groups C and S,MWT was significantly decreased at 7-21 days after inoculation,the expression of p-ERK5 and Fos protein was significantly up-regulated at 5-21 days after inoculation (P ＜ 0.05),and no significant change was found in the expression of ERK5 in group BCP (P ＞ 0.05).Conclusion Intra-tibial inoculation of Walker-256 breast cancer cells can increase the activity of ERK5 in the spinal cord in rats,leading to the increased release of Fos protein,thus inducing BCP.