鞘内注射Staurosporine对骨癌痛大鼠脊髓小胶质细胞活化的影响  

Effect of intrathecal injection of Staurosporine on spinal microglia activation in rats with bone cancer pain

作　　者：陈勇[1] 杜晓红[1] 应俊[1] 童希忠 梁应平[1] 胡衍辉[1] 徐国海[1] 

机构地区：[1]南昌大学第二附属医院麻醉科,330006

出　　处：《临床麻醉学杂志》2013年第12期1214-1217,共4页Journal of Clinical Anesthesiology

摘　　要：目的观察鞘内注射蛋白激酶C（PKC）抑制剂Staurosporine对胫骨骨癌痛大鼠机械痛行为和脊髓小胶质细胞活化的影响。方法健康成年雄性SD大鼠120只，200-250g，采用随机数字表法分为五组，每组24只。除C组外，其他四组均制备胫骨骨癌痛模型。模型制备后第10-12天，N组、S组和SP组分别于鞘内注入生理盐水、二甲基亚砜（DMSO）或Staurosporine 10μl，每天1次，连续3d。M组鞘内不给予任何药物。记录鞘内给药前（T0）、给药后1d（T1）、3d（T2）、5d（T3）、7d（T1）、10d（T5）、14d（T6）和21d（T1）的机械缩足阈值（MWT）和缩足热潜伏期（WTL）。并采用免疫组织化学方法测定脊髓背角小胶质细胞特异表达补体C3受体（OX-42）及离子钙接头蛋白分子-1（Iba-1）的表达。结果与C组比较，M组、N组、S组及SP组MWT明显降低，WTL明显缩短（P〈0．05）。与M组比较，S组和SP组MWT明显升高，WTL明显延长（P〈0．05）。与S组比较，SP组MwT明显升高，wTL明显延长（P〈0．05）。C组脊髓背角OX-42及Iba〉1染色较浅，未发现小胶质细胞。T0和T7时M组、N组、s组和sP组OX-42和Iba-1表达差异无统计学意义。与，T0时比较，T1～T5时M组、N组、S组和SP组大鼠脊髓背角OX-42、Iba-1表达明显升高（P〈0．05）。与M组比较，T1～T6时s组和SP组大鼠脊髓背角OX-42和Iba-1表达明显降低（P〈0．05）。与s组比较，T1～T5时SP组脊髓背角OX-42和Iba-1表达明显降低（P〈0．05）。结论鞘内注射Stauros—porine可抑制大鼠脊髓小胶质细胞的活化从而减轻骨癌痛。Objective To investigate the effect of intrathecal injection with PKC inhibitor Staurosporine on pain behaviors and spinal microglia activation in rats with shin bone cancer pain. Methods One hundred and twenty adult male SD rats weighting 200-250 g were randomly divided into 5 groups （n=24） ..control group （group C） ,model group （group M）, normal saline group （group N）, solvent group （group S） and Staurosporine group （group SP）. Bone cancer pain was induced by intra-tibia inoculation of Walker256 mammary gland carcinoma cells in groups M, N, S and SP. Imrathecal injection wasapplied after 10 days, once a day, andcontinued for three days. Group N received imrathecal injection of normal saline 10 /11, and group S receivedintrathecal injection of DMSO 10 /11. Rats in group SP receivedintrathecal injection of Staurosporine 10μl. Pain behaviors were assessed before injection （To） and on 1 d（Tl ）, 3 d（T2 ）, 5 d（T3 ）, 7 d（T4 ）, 10 d（T5）, 14 d（T6 ）and 21 days（T7 ） after injections. Three rats were sacrificed at each time point in each group for detecting the expression of OX 42 and Iba-1 in the spinal dorsal horn by immunofluorescenc〈 Results When compared with group C, paw mechanical withdrawal threshold （MWT） and paw withdrawal thermal latency （WTL）were significantly decreased in the other 4 groups（P〈0. 05 ）. The WMT and WTL were significantly increased in group S and SP, while the expressions of OX-42 and Iba-1 in the spinal dorsal horn in these two groups were decreased when compared with group M（P〈0. 05）. Compared with group S, the WMT and the WI＇L in group SP were significantly increased and the expression of OX-42 and Iba-1 in the spinal dorsal horn in group SP was decreased（P〈0. 05）. Conclusion The intrathecal injection of Staurosporine may reduce pain behaviors and inhibitthe spinal microglia activation in a rat model of bone cancer pain.

关 键 词：蛋白激酶C抑制剂 骨肿瘤 小神经胶质细胞 

分 类 号：R738[医药卫生—肿瘤]