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

Influences of intrathecal fluorocitrate and/or minocycline injection on tumour growth and pain in bone cancer mouse model

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小鼠按配伍组设计随机法分为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21d，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。结果术前当天各组小鼠的疼痛刺激缩足反应差异无统计学意义（P〉0．05）；与正常组及基础值相比，术后3d假手术组小鼠疼痛刺激缩足反应显著变化（P〉0．05）；而癌痛组小鼠疼痛刺激缩足反应显著增加（P〈0．05）。其中癌痛组内，与ACSF组相比，术后5dMI组小鼠疼痛刺激缩足反应显著降低（P〈0．05）；MI＋FC组小鼠刺激性缩足反应也显著降低（P〈0．01）；而FC组术后10d小鼠刺激性缩足反应显著降低（P〈0．05）。术前当天各组组间基础体重差异无统计学意义（P〉0．05）。与正常组相比，假手术组和癌痛组小鼠的体重在术后3d虽有所下降，但差异无统计学意义（P〉0．05）。与正常组相比，术后21d癌痛组小鼠体重显著降低（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差异无统计学意义。结论鞘内同时注射氟代柠檬酸和／或米诺四环素明显降低癌痛小鼠的缩足反应，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。

Objective To study the influences of intrathecal injection of a＇strocytes inhibitor fluorocitrate （FC） and/or microglia inhibitor minocycline （MI） on on tumour growth and pain in bone cancer mouse model. Methods C3H/He mice suffering from bone cancer were intrathecally injected with nothing, artificial CSF, FC, MI, or FC＋MI. Behaviour, body weight, bone tumor biopsy was observed or detected. Results Results On the preoperative day, paw withdrawal response of mice in each group was no significant different （P〉0.05）; compared with the normal group and the baseline, on the 3rd day after operation, the paw withdrawal response of mice in sham-operated group was no significant changed （P〉0.05） ; compared with normal group, on the 3rd day after operation, the paw withdrawal response was significantly increased（P〈0.05 ）. And compared with ACSF group, on the 5th day after operation, the paw withdrawal response of mie in the group FC＋MI, was significantly decreased （P〈0.01）, and was also significantly decreased in the group MI （P〈 0.05 ）. On the lOth day after operation, the paw withdrawal response was significantly decreased in the group FC（P〈0.05 ）. On the preoperative day, the basis of body weight in each group was no significant different （P〉0.05）. Compared with normal group, the body weight of mice on the 3rd day after operation in sham-operated group and the cancer pain groups reduced somewhat, but there were no statistical significances （P〉0.05）. Compared with normal group, body weight of mice on the 21th day after operation in the cancer pain groups decreased significantly （P〈0.05） ; compared with the ACSF group, MI group, FC group and MI ＋ FC group, the body weight of mice was less reduced, there were statistical significances （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 Intrathecal fluorocitrate and/or minocycline injection can increase the pain threshold, thereby inhibiting hyperalgesia and pain high-sensitivity, without influence on tumor growth and bone damage extent in bone cancer mouse model.