国际麻醉学与复苏杂志   2010, Issue (2): 106-110
    
鞘内注射氟代柠檬酸和/或米诺四环素对骨癌痛小鼠疼痛及肿瘤的影响
孙玉娥 申文 唐元章 苏小虎1()
1.221002 徐州,江苏省麻醉学重点实验室
Effect of intrathecal fluorocitrate and /or minocycline on pain and tumour in a murine model of bone cancer pain
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摘要:

目的 研究鞘内注射星形胶质细胞抑制剂氟代柠檬酸(fluorocitrate,FC)和/或小胶质细胞特异性抑制剂米诺四环素(minocycline,MI)对C3H/He小鼠跟骨癌性疼痛及肿瘤的影响。方法 将雄性C3H/He小鼠随机分为6组(n=20),包括:正常组、假手术组、癌痛+人工脑脊液组(artificial cerebrospinal fluid,ACSF)、癌痛+FC组、癌痛+MI组、癌痛+FC+MI组。术后每天给药1次,持续21 d,并于术前当天、术后3、5、7、10、14、21d采用机械性痛觉过敏行为学及冷痛敏测定小鼠行为学变化,天平秤称量小鼠体重变化及组织切片HE染色观察肿瘤骨的骨质破坏程度。结果 术后3 d始癌痛组出现痛觉增敏及痛觉超敏。其中癌痛组内,与鞘内注射ACSF组相比,术后第5天始MI组小鼠疼痛阈值明显提高(P<0.05);MI+FC组小鼠疼痛阈值也明显提高(P<0.01);而FC组术后第10天始小鼠疼痛阈值明显提高(P<0.05)。术后21 d癌痛组体重明显降低,低于正常组(P<0.05);与ACSF组相比,MI组、FC组及MI+FC组体重降低较少(P<0.05)。同时间点内,癌痛各组间组织切片HE 染色发现肿瘤的大小及骨的破坏程度无明显差异。结论 鞘内同时注射FC和/或MI明显提高癌痛小鼠的疼痛阈值,抑制其痛觉过敏或痛觉超敏的产生,改善骨癌痛小鼠体重的变化,但对肿瘤本身的生长及组织的破坏程度无影响。

关键词: 骨癌痛;米诺四环素;氟代柠檬酸;行为学;组织学
Abstract:

Objective To study the effect of intrathecal injecting (i.t.) astrocytes inhibitor fluorocitrate (FC) and /or microglia inhibitor minocycline (MI) on pain and tumour in a murine model of bone cancer pain. Methods C3H/He mice with intrathecal catheter insertion and checkouted by lidocaine experiment randomly was divided into six groups (n=20) which included normal group, sham group, cancer pian group (received tumour cells inserted into the left calcaneus bone marrow cavity )+ Artificial CSF group, FC group, MI group, FC + MI group. One day after administration, continued for 21 days, and before and on the 3rd,5th,7th,10th,14th,21th day after operation, the mice were tested by mechanical behavior of high-sensitivity, determination Lengtong-mouse behavior, weighing the body weight and observed the bone damage of bone tumor by biopsy HE staining. Results Compared with normal group, on the 3rd day after operation, the cancer pain group had obvious statistical significance. And compared with ACSF group, on the 5th day after operation, the group intrathecal FC+MI, the pain threshold was significantly increased (P<0.01), the group intrathecal MI the pain threshold was also significantly increased (P<0.05). On the 14th day after operation, the group intrathecal FC, the pain threshold was significantly increased (P<0.05). Compared with normal group, the cancer pain group body weight decreased significantly (P<0.05); compared with the with the ACSF group, MI group, FC group and MI + FC group, the body weight of mice was reduced less, there was statistical significance (P<0.05). At the same time point, compared with each other, there was no significance within the cancer pain groups, through the tumor size and bone mass of the extent of the damage. Conclusion During the test dose, while mice were intrathecal fluorinated citric acid and / or minocycline can increase the pain threshold, thereby inhibiting its hyperalgesia and pain of a high-sensitivity, also it can inhibit the reduction of body weigh, but it had no effect on tumor growth and the extent of damage.

Key words: Bone cancer pain; Fluorocitrate; Minocycline; Behavior; Histology