CAJ | 학술논문

目的评价脊髓趋化因子CXCL12在大鼠骨癌痛形成中的作用及其与小胶质细胞活化的关系.方法清洁级成年雌性SD大鼠32只,体重180 ～ 220 g,采用随机数字表法分为4组(n=8):假手术组(S组)、骨癌痛组(B组)、骨癌痛+ CXCL12中和抗体组(BC组)和骨癌痛+IgG对照抗体组(BI组).B组、BC组和B组大鼠右侧胫骨骨髓腔注入Walker 256乳腺癌细胞5μl(4×105个/ml)；S组大鼠右侧胫骨骨髓腔注入5μl生理盐水；于注射乳腺癌细胞后第12、13和14天,BC组鞘内注射CXCL12中和抗体(10 μg/15μl,1次/d),BI组鞘内注射IgG对照抗体(10 μg/15μl,1次/d).于注射乳腺癌细胞前(T0)、注射后3、5、7、10、12和14 d(T1-6)时测定机械痛阈,于T6时痛阈测定结束后取大鼠L45脊髓,采用免疫荧光技术检测脊髓背角小胶质细胞标记物Iba-1的表达.结果与S组比较,B组、BC组和BI组T2-6时机械痛阈降低,T6时脊髓背角Iba-1表达上调(P＜0.01)；与B组比较,BC组T56时机械痛阈升高,T6时脊髓背角Iba-1表达下调(P＜0.01).结论脊髓趋化因子CXCL12参与了大鼠骨癌痛的形成,其机制与小胶质细胞活化有关.
목적 평개척수추화인자CXCL12재대서골암통형성중적작용급기여소효질세포활화적관계.방법 청길급성년자성SD대서32지,체중180 ～ 220 g,채용수궤수자표법분위4조(n=8):가수술조(S조)、골암통조(B조)、골암통+ CXCL12중화항체조(BC조)화골암통+IgG대조항체조(BI조).B조、BC조화B조대서우측경골골수강주입Walker 256유선암세포5μl(4×105개/ml)；S조대서우측경골골수강주입5μl생리염수；우주사유선암세포후제12、13화14천,BC조초내주사CXCL12중화항체(10 μg/15μl,1차/d),BI조초내주사IgG대조항체(10 μg/15μl,1차/d).우주사유선암세포전(T0)、주사후3、5、7、10、12화14 d(T1-6)시측정궤계통역,우T6시통역측정결속후취대서L45척수,채용면역형광기술검측척수배각소효질세포표기물Iba-1적표체.결과 여S조비교,B조、BC조화BI조T2-6시궤계통역강저,T6시척수배각Iba-1표체상조(P＜0.01)；여B조비교,BC조T56시궤계통역승고,T6시척수배각Iba-1표체하조(P＜0.01).결론 척수추화인자CXCL12삼여료대서골암통적형성,기궤제여소효질세포활화유관.
Objective To evaluate the role of chemokine CXCL12 in the spinal cord in the development of bone cancer pain (BCP) in rats and the relationship with microglial activation.Methods Thirty-two female Sprague-Dawley rats,weighing 180-220 g,were equally randomized into 4 groups (n =8 each) using a random number table:sham operation group (group S),BCP group (group B),BCP + CXCL12 neutralizing antibody group (group BC),and BCP + IgG control antibody group (group BI).BCP was induced by injecting Walker 256 mammary gland cancer cell suspension (4 × 105 cells/ml) 5 μl into the bone marrow of the right tibia of rats anesthetized with chloral hydrate in B,BC and BI groups,while the equal volume of normal saline was injected instead in group S.On 12,13 and 14 days after injection of mammary gland cancer cells,CXCL12 neutralizing antibody 10 μg/15 μl was intrathecally injected once a day in group BC,while IgG control antibody 10 μg/15 μl was intrathecally injected once a day in group BI.Before injection of mammary gland cancer cells (T0) and on 3,5,7,10,12 and 14 days after injection of mammary gland cancer cells (T16),paw withdrawal threshold to mechanical stimulation (PWMT) was measured.The rats were then sacrificed and L4,5 segments of the spinal cord were removed for determination of Iba-1 (pan-microglial marker) expression in spinal dorsal horn using immunofluorescence after PWMT measurement at T6.Results Compared with S group,PMWT was significantly decreased at T2-6,and Iba-1 expression was up-regulated at T6 in B,BC and BI groups (P ＜ 0.01).Compared with B group,PMWT was significantly increased at T5,6 and Iba-1 expression was down-regulated at T6 in BC group (P ＜ 0.01).Conclusion Chemokine CXCL12 in the spinal cord is involved in the development of BCP,and microglial activation is involved in the mechanism.