中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2011年
17期
1188-1192
,共5页
王丽娜%杨建平%嵇富海%王秀云%左剑玲%许期年%贾晓明%周静%任春光%李伟
王麗娜%楊建平%嵇富海%王秀雲%左劍玲%許期年%賈曉明%週靜%任春光%李偉
왕려나%양건평%혜부해%왕수운%좌검령%허기년%가효명%주정%임춘광%리위
骨肿瘤%疼痛%脑源性神经营养因子%脊髓
骨腫瘤%疼痛%腦源性神經營養因子%脊髓
골종류%동통%뇌원성신경영양인자%척수
Bone neoplasms%Pain%Brain-derived neurotrophic factor%Spinal cord
目的 探讨脑源性神经牛长因子(BDNF)及其下游磷酸化细胞外信号调节蛋白激酶1/2(p-ERK1/2)在骨癌痛中的作用及其脊髓机制.方法 雌性SD大鼠60只,随机分为5组(n=12),Ⅰ组为模型对照组,Ⅱ组为骨痛痛组,Ⅲ组为模型对照组+BDNF中和抗体,Ⅳ组为骨痛痛组+IgG对照抗体;Ⅴ组为骨癌痛组+BDNF中和抗体.Ⅱ、Ⅳ和Ⅴ组于大鼠左胫骨上端注入Walker256 细胞,制备骨痛痛模型;模型对照组大鼠左胫骨上端注入Hank's液.造模后第7～9天,Ⅲ、Ⅳ和Ⅴ组鞘内分别注射BDNF中和抗体、IgG对照抗体和BDNF中和抗体15μg/10μl,1次/d,连续3 d.分别于术前及术后隔日开始测定大鼠Von-Frey阈值,并测定脊髓后角的BDNF和p-ERK1/2表达水平.结果 BDNF和p-ERK1/2在脊髓后角有共表达;术后第6～18天,与Ⅰ组比较,Ⅱ、Ⅳ组Von-Fray阈值显著下降;术后第9天,脊髓BDNF和p-ERK1/2的蛋白表达显著增加(均P<0.01);Ⅲ组上述指标的差异无统计学意义(P>0.05);与Ⅱ、Ⅳ组比较,Ⅴ组Von-Frey阈值显著增高,脊髓BDNF和p-ERK1/2的蛋白表达显著减少(均P<0.01).结论 内源性BDNF可能通过其下游的p-ERK1/2信号转导途径参与了骨癌痛大鼠痛觉过敏的形成.
目的 探討腦源性神經牛長因子(BDNF)及其下遊燐痠化細胞外信號調節蛋白激酶1/2(p-ERK1/2)在骨癌痛中的作用及其脊髓機製.方法 雌性SD大鼠60隻,隨機分為5組(n=12),Ⅰ組為模型對照組,Ⅱ組為骨痛痛組,Ⅲ組為模型對照組+BDNF中和抗體,Ⅳ組為骨痛痛組+IgG對照抗體;Ⅴ組為骨癌痛組+BDNF中和抗體.Ⅱ、Ⅳ和Ⅴ組于大鼠左脛骨上耑註入Walker256 細胞,製備骨痛痛模型;模型對照組大鼠左脛骨上耑註入Hank's液.造模後第7～9天,Ⅲ、Ⅳ和Ⅴ組鞘內分彆註射BDNF中和抗體、IgG對照抗體和BDNF中和抗體15μg/10μl,1次/d,連續3 d.分彆于術前及術後隔日開始測定大鼠Von-Frey閾值,併測定脊髓後角的BDNF和p-ERK1/2錶達水平.結果 BDNF和p-ERK1/2在脊髓後角有共錶達;術後第6～18天,與Ⅰ組比較,Ⅱ、Ⅳ組Von-Fray閾值顯著下降;術後第9天,脊髓BDNF和p-ERK1/2的蛋白錶達顯著增加(均P<0.01);Ⅲ組上述指標的差異無統計學意義(P>0.05);與Ⅱ、Ⅳ組比較,Ⅴ組Von-Frey閾值顯著增高,脊髓BDNF和p-ERK1/2的蛋白錶達顯著減少(均P<0.01).結論 內源性BDNF可能通過其下遊的p-ERK1/2信號轉導途徑參與瞭骨癌痛大鼠痛覺過敏的形成.
목적 탐토뇌원성신경우장인자(BDNF)급기하유린산화세포외신호조절단백격매1/2(p-ERK1/2)재골암통중적작용급기척수궤제.방법 자성SD대서60지,수궤분위5조(n=12),Ⅰ조위모형대조조,Ⅱ조위골통통조,Ⅲ조위모형대조조+BDNF중화항체,Ⅳ조위골통통조+IgG대조항체;Ⅴ조위골암통조+BDNF중화항체.Ⅱ、Ⅳ화Ⅴ조우대서좌경골상단주입Walker256 세포,제비골통통모형;모형대조조대서좌경골상단주입Hank's액.조모후제7～9천,Ⅲ、Ⅳ화Ⅴ조초내분별주사BDNF중화항체、IgG대조항체화BDNF중화항체15μg/10μl,1차/d,련속3 d.분별우술전급술후격일개시측정대서Von-Frey역치,병측정척수후각적BDNF화p-ERK1/2표체수평.결과 BDNF화p-ERK1/2재척수후각유공표체;술후제6～18천,여Ⅰ조비교,Ⅱ、Ⅳ조Von-Fray역치현저하강;술후제9천,척수BDNF화p-ERK1/2적단백표체현저증가(균P<0.01);Ⅲ조상술지표적차이무통계학의의(P>0.05);여Ⅱ、Ⅳ조비교,Ⅴ조Von-Frey역치현저증고,척수BDNF화p-ERK1/2적단백표체현저감소(균P<0.01).결론 내원성BDNF가능통과기하유적p-ERK1/2신호전도도경삼여료골암통대서통각과민적형성.
Objective To investigate the role of brain-derived neurotrophic factor(BDNF)in pain facilitation and spinal mechanisms in the rat model of bone cancer pain.Methods The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity.Sixty SD female rats were divided into 5 groups(n=12 each)randomly;group Ⅰ:contrrol group (sham operation);group Ⅱ;model group;group Ⅲ:control group+anti-BDNF intrathecal(i.t.);group Ⅳ:modeI group+control IgG i.t.;group Ⅴ:model group+anti-BDNF i.t..Anti-BDNF or control IgG was injected i.t. during 7 to 9th day.Von-Frey threshold was measured one day before operation and every 2 days after operation.On the 9th day after threshold tested,rats were sacrificed after i.t. injection of either antiBDNF or control IgG,the lumbar 4-6 spinal cord was removed.The expression of the spihal BDNF and the phosphorylation of extracellular signal-regulated protein kinase1/2(p-ERK1/2)were detected by immunohistochemistry assay and Western-Blot.Co-expression pattern of BDNF and p-ERK1/2 were determined by double-labeling immunofluorescence.Results We demonstrated the coexistence of BDNF and p-ERK1/2 in the spinal cord of rats. From the 7 to 9th day after operation,von-Frey threshold in groups Ⅱ and Ⅳ was significantly lower than that in group Ⅰ and group Ⅴ(P<0.01),group Ⅴ was remarklv higher than that in group Ⅳ(P<0.01).'The spinal BDNF and p-ERK1/2 expression in group Ⅱ or Ⅳ were significantly increased compared with that in group Ⅰ or Ⅴ(P<0.01),intrathceal anti-BDNF was significantly suppressed BDNF and P-ERK1/2 expression(P<0.01).Conclusion BDNF and p-ERK1/2 was coexistence in the spinal cord of rats,and it maybe involved in the bone cancer pain.
