中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2010年
2期
165-169
,共5页
刘思兰%杨建平%王丽娜%刘磊%李彩芳%任春光%周静%李伟%江淼%马珍妮%邱桥成
劉思蘭%楊建平%王麗娜%劉磊%李綵芳%任春光%週靜%李偉%江淼%馬珍妮%邱橋成
류사란%양건평%왕려나%류뢰%리채방%임춘광%주정%리위%강묘%마진니%구교성
骨肿瘤%疼痛%Toll样受体4%肿瘤坏死因子α%白细胞介素1β
骨腫瘤%疼痛%Toll樣受體4%腫瘤壞死因子α%白細胞介素1β
골종류%동통%Toll양수체4%종류배사인자α%백세포개소1β
Bone neoplasms%Pain%Toll-like receptor 4%Tumor necrosis factor-alpha%Interleukin-1beta
目的 评价胫骨癌痛大鼠脊髓Toll样受体4(TLR4)及其下游细胞因子(TNF-α和IL-1β)表达的变化,探讨TLB4信号转导通路在骨癌痛中的作用.方法 健康雌性SD大鼠72只,体重150～180 g,随机分为3组(n=24):正常对照组(C组)、假手术组(S组)和胫骨癌痛组(BP组).BP组于大鼠左侧胫骨干骺端骨髓腔内注射5μl Walker 256(1×10~5)乳腺癌细胞制备胫骨癌痛模型,S组仅左侧胫骨上端注入Hank液5μl.于接种前(基础状态)、接种后2、4、6、9、12、14、16、18和21 d时行痛行为学评分,测定机械痛阈.于接种后6、12、18 d时行胫骨X线摄片,观察胫骨破坏情况,并于各时点取3只大鼠,处死后取L_(4～6)脊髓,测定TLR4、TNF-α和IL-1β的mRNA表达,各时点另取3只大鼠,处死后取L_(4～6)脊髓,计数TLR4阳性细胞;测定TLR4蛋白表达.结果 与基础值比较,BP组接种后6～21 d时痛行为学评分逐渐升高,机械痛阈逐渐降低(P＜0.05),C组和S组各时点痛行为学评分差异无统计学意义(P＞0.05).与C组和S组比较,BP组痛行为学评分升高,机械痛阈降低,TLR4 mRNA和蛋白、TNF-α mRNA和IL-1β mRNA表达上调,TLR4 阳性细胞计数增多(P＜0.05或0.01).BP组接种后6 d即可见左侧胫骨上端骨小梁轻微缺损,12 d时多处骨小梁缺损,骨皮质破坏,18 d时胫骨上端双侧骨皮质明显破坏,大片骨质缺损.结论 大鼠胫骨骨髓腔内肿瘤细胞通过激活脊髓TLR4,导致其下游细胞因子大量释放,而诱发骨癌痛.TLR4可能是胫骨癌痛潜在治疗靶点.
目的 評價脛骨癌痛大鼠脊髓Toll樣受體4(TLR4)及其下遊細胞因子(TNF-α和IL-1β)錶達的變化,探討TLB4信號轉導通路在骨癌痛中的作用.方法 健康雌性SD大鼠72隻,體重150～180 g,隨機分為3組(n=24):正常對照組(C組)、假手術組(S組)和脛骨癌痛組(BP組).BP組于大鼠左側脛骨榦骺耑骨髓腔內註射5μl Walker 256(1×10~5)乳腺癌細胞製備脛骨癌痛模型,S組僅左側脛骨上耑註入Hank液5μl.于接種前(基礎狀態)、接種後2、4、6、9、12、14、16、18和21 d時行痛行為學評分,測定機械痛閾.于接種後6、12、18 d時行脛骨X線攝片,觀察脛骨破壞情況,併于各時點取3隻大鼠,處死後取L_(4～6)脊髓,測定TLR4、TNF-α和IL-1β的mRNA錶達,各時點另取3隻大鼠,處死後取L_(4～6)脊髓,計數TLR4暘性細胞;測定TLR4蛋白錶達.結果 與基礎值比較,BP組接種後6～21 d時痛行為學評分逐漸升高,機械痛閾逐漸降低(P＜0.05),C組和S組各時點痛行為學評分差異無統計學意義(P＞0.05).與C組和S組比較,BP組痛行為學評分升高,機械痛閾降低,TLR4 mRNA和蛋白、TNF-α mRNA和IL-1β mRNA錶達上調,TLR4 暘性細胞計數增多(P＜0.05或0.01).BP組接種後6 d即可見左側脛骨上耑骨小樑輕微缺損,12 d時多處骨小樑缺損,骨皮質破壞,18 d時脛骨上耑雙側骨皮質明顯破壞,大片骨質缺損.結論 大鼠脛骨骨髓腔內腫瘤細胞通過激活脊髓TLR4,導緻其下遊細胞因子大量釋放,而誘髮骨癌痛.TLR4可能是脛骨癌痛潛在治療靶點.
목적 평개경골암통대서척수Toll양수체4(TLR4)급기하유세포인자(TNF-α화IL-1β)표체적변화,탐토TLB4신호전도통로재골암통중적작용.방법 건강자성SD대서72지,체중150～180 g,수궤분위3조(n=24):정상대조조(C조)、가수술조(S조)화경골암통조(BP조).BP조우대서좌측경골간후단골수강내주사5μl Walker 256(1×10~5)유선암세포제비경골암통모형,S조부좌측경골상단주입Hank액5μl.우접충전(기출상태)、접충후2、4、6、9、12、14、16、18화21 d시행통행위학평분,측정궤계통역.우접충후6、12、18 d시행경골X선섭편,관찰경골파배정황,병우각시점취3지대서,처사후취L_(4～6)척수,측정TLR4、TNF-α화IL-1β적mRNA표체,각시점령취3지대서,처사후취L_(4～6)척수,계수TLR4양성세포;측정TLR4단백표체.결과 여기출치비교,BP조접충후6～21 d시통행위학평분축점승고,궤계통역축점강저(P＜0.05),C조화S조각시점통행위학평분차이무통계학의의(P＞0.05).여C조화S조비교,BP조통행위학평분승고,궤계통역강저,TLR4 mRNA화단백、TNF-α mRNA화IL-1β mRNA표체상조,TLR4 양성세포계수증다(P＜0.05혹0.01).BP조접충후6 d즉가견좌측경골상단골소량경미결손,12 d시다처골소량결손,골피질파배,18 d시경골상단쌍측골피질명현파배,대편골질결손.결론 대서경골골수강내종류세포통과격활척수TLR4,도치기하유세포인자대량석방,이유발골암통.TLR4가능시경골암통잠재치료파점.
Objective To investigate the changes in the expression of Toll-like receptor 4(TLR4)and its downstream cytokines TNF-α and IL-1β in the spinal cord in a rat model of bone cancer pain.Methods Seventy-two female SD rats weighing 150-180 g were randomly divided into 3 groups(n = 24 each): group Ⅰ normal control(group C);group Ⅱ sham operation(group S)and group Ⅲ bone cancer pain(group BP).Bone cancer was induced by intra-tibial inoculation of 1× 10~5 Walker 256 breast cancer cells.Bone cancer and bone destruction were shown by X-ray.Paw withdrawal threshold (PWT) to mechanical stimulation was measured with von Frey filaments and spontaneous pain was evaluated by ambulatory score.The expression of TLR4,TNF-α and IL-1βmRNA in the spinal cord was determined by RT-PCR and the expression of TLR4 protein by immuno-histochemistry and TLR4 positive cell count was determined.Results In group BP the ambulatory score started increasing and PWT to mechanical stimulation started decreasing at 6 days after inoculation.The ambulatory score was significantly higher,PWT significantly lower and the expression of TLR4 mRNA and protein and TNF-α and IL-1β mRNA in the spinal cord and TLR4 positive cell count were significantly higher in group BP than in group C and S.Conclusion Intra-tibial inoculation of Walker 256 breast cancer cells activates TLR4 in the spinal cord,leading to the increased release of its downstream cytokines and mechanical hyperalgesia.TLR4 might be a potential target for the treatment of bone cancer pain.
