CAJ | 학술논문

目的观察导水管周围灰质内注射黑皮质素受体4型(MC4R)拮抗剂对骨癌痛模型大鼠疼痛行为学及腰段脊髓星形胶质细胞活化的影响,探讨其治疗骨癌痛的机制.方法选择雌性SD大鼠18只,随机分为3组(n=6):A组(对照组):左侧胫骨上段骨髓腔注入3μl生理盐水(NS);B组(模型组):左侧胫骨上段骨髓腔注入3μl MRMT-1大鼠乳腺癌细胞(1×103/μl),导水管周围灰质(PAG)内注射NS 0.5μl;C组(HS014组):造模同B组,PAG内注射MC4R拮抗剂HS0140.5μl.术后每24 h在PAG内注射HS014(0.5 μg/0.5μl)或NS 1次,连续注射至术后13 d.大鼠与术前及术后1、3、7、14 d给药后60 min内,采用热板测痛仪测试大鼠的热痛阈值.第14天取大鼠脊髓L4～L6节段,采用免疫组织化学方法观察骨癌痛大鼠腰段脊髓星形胶质细胞阳性产物分布及变化.结果 A组大鼠对热痛阈值在术后各时间点组内比较差异无统计学意义(P＞0.05);B、C组大鼠对热痛阈值在术后的前6d与A组比较升高(P＜0.05);术后7～14d,与B组大鼠对热痛阈值比较,C组明显降低(P＜0.05).大鼠腰脊髓背角胶质纤维酸性蛋白(GFAP)免疫反应吸光度值C组(50.15 ±1.98)比B组(59.46 ±2.55)降低(P＜0.05).结论导水管周围灰质内注射MC4R拮抗剂HS014抑制乳腺癌骨转移模型大鼠骨癌痛,其机制可能是抑制脊髓星形胶质细胞激活.
목적 관찰도수관주위회질내주사흑피질소수체4형(MC4R)길항제대골암통모형대서동통행위학급요단척수성형효질세포활화적영향,탐토기치료골암통적궤제.방법 선택자성SD대서18지,수궤분위3조(n=6):A조(대조조):좌측경골상단골수강주입3μl생리염수(NS);B조(모형조):좌측경골상단골수강주입3μl MRMT-1대서유선암세포(1×103/μl),도수관주위회질(PAG)내주사NS 0.5μl;C조(HS014조):조모동B조,PAG내주사MC4R길항제HS0140.5μl.술후매24 h재PAG내주사HS014(0.5 μg/0.5μl)혹NS 1차,련속주사지술후13 d.대서여술전급술후1、3、7、14 d급약후60 min내,채용열판측통의측시대서적열통역치.제14천취대서척수L4～L6절단,채용면역조직화학방법관찰골암통대서요단척수성형효질세포양성산물분포급변화.결과 A조대서대열통역치재술후각시간점조내비교차이무통계학의의(P＞0.05);B、C조대서대열통역치재술후적전6d여A조비교승고(P＜0.05);술후7～14d,여B조대서대열통역치비교,C조명현강저(P＜0.05).대서요척수배각효질섬유산성단백(GFAP)면역반응흡광도치C조(50.15 ±1.98)비B조(59.46 ±2.55)강저(P＜0.05).결론 도수관주위회질내주사MC4R길항제HS014억제유선암골전이모형대서골암통,기궤제가능시억제척수성형효질세포격활.
Objective To investigate the effects of melanocortin-4 receptor antagonist HS014 on astrocyte activation of spinal cord in bone cancer pain rats.Methods Eighteen SD female rats weighing 180-220 g were randomly divided into 3 groups (n =6 each):A group(control group):intra-tibial injection of 3 μl saline;B group (model group):intra-periqueductal gray (PAG) injection of 0.5 μl saline after intra-tibial injection of 3 μl MRMT-1 cells (1 × 103/μl) ; C group (HS014 group):intra-PAG injection of 0.5 μl MC4R antagonist HS014 after intra-tibial injection of 3 μl MRMT-1 cells.From 1h of intra-tibial operation,0.5 μl saline or HS014 were injected into PAG respectively per day for 14 days.Heat threshold of rats' hind paws were measured every other day from one day before operation until 14 days later.The lumbar 4-6 spinal cord was removed on 14d after operation.The changes of the spinal glial fibrillary acidic protein (GFAP) immunoreactivity were detected by immunohistochemistry method.Results No significant differences in heat threshold were found at all time points in A group.During the first 6 days of postoperation there were obvious differences in heat stimulus between A and the other groups (P ＜ 0.05) ; During 7-14 d after operation,heat threshold in A and C group were significantly different from those of B group (P ＜ 0.05),but the differences were not remarkable between A and C group.The absorbance value of GFAP immunoreactivity in B group (59.46 ± 2.55) showed stronger staining than that in C group (50.15 ± 1.98) (P ＜ 0.05).No significant difference of GFAP immunoreactivity was found between C group and A group (P ＞ 0.05).Conclusion Intra-PAG injection of MC4R antagonist HS014 inhibits bone cancer pain in rats by repressing spinal astrocyte activation.