摘要
目的:观察N-甲基-D-天门冬氨酸(NMDA)受体2B亚型(NR2B)选择性拮抗剂Ro25-6981对胫骨癌痛大鼠脊髓后角星型胶质细胞的影响,探讨骨癌痛的发生机制。方法:采用Walker256乳腺癌细胞建立雌性SD大鼠胫骨癌痛模型。将大鼠随机分为3组(每组8只):假手术组(Sham组)、模型组(M组)和Ro25-6981组(R组)。假手术组只行鞘内置管,模型组鞘内注射(IT)生理盐水20μl,Ro25_6981组于建立大鼠骨癌痛模型前30 min及术后第7天IT Ro25-6981 20μl(0.5 mg/ml)。Sham组于假手术后3 d及R组和M组均于术后14 d分别取8只大鼠,测定机械痛阈阈值后断头处死,取患侧L4-6脊髓背角组织,采用免疫组化方法观察GFAP、OX-42及NR2B的表达变化判断Ro25-6981对脊髓背角星形胶质细胞及小胶质细胞活化的影响。结果:各组术前基础机械痛阈比较差异无统计学意义(P>0.05)。与Sham组比较,M组术后14 d时机械痛阈降低(P<0.01),Ro25-6981组术后14 d时机械痛阈降低,差异有统计学意义(P<0.05);与模型组比较,Ro25-6981组术后14 d时机械痛阈升高(P<0.05)。与Sham组相比,Ro25-6981组和M组术后14 d时脊髓背角GFAP、OX-42和NR2B蛋白表达均升高(P<0.05);与M组比较,R组术后14 d时脊髓背角GFAP、OX-42和NR2B蛋白表达降低(P<0.05)。结论:鞘内注射Ro25-6981可抑制脊髓背角星形胶质细胞和/或小胶质细胞激活,有效地预防大鼠胫骨癌痛的发生及发展。
Objective：To investigate the effect of Ro25-6981 on spinal astrocytes and microglia in the tibia1 cancer rats. The changes of spinal astrocytes and gitter cells were detected by immunohistochemistry , Weston-blot and real-time PCR. Methods： （ expression of GFAP, OX-42 and NR2B ）. In R and M groups PWPT was significantly decreased compared with Sham group, the expression of GFAP , OX-42 protein and NR2B were significantly higher than Sham group. In R group PWPT and the expression of GFAP, OX-42 protein and NR2B were significantly increased compared with group M. Results： The results suggested that low dose Ro25-6981 can attenuate the cancer pain to inhibit the activation of astrocytes and gitter cells by inhibiting the expression of NMDA- NR2B in the spinal cord. Conclusion：
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2014年第9期1208-1212,共5页
Chinese Journal of Immunology
基金
国家自然科学基金(No. 81171057)
江苏省自然科学基金(No. SBK201121879)
