C57BL/6小鼠骨癌痛模型的制备与评价

目的:探讨用Lewis肺癌细胞系制备C57BL/6小鼠股骨癌痛动物模型的可行性.方法:选用体质量18～20 g雄性C57BL/6小鼠60只,随机分为4组(n=15).实验组接种Lewis肺癌细胞2×106个;热灭活组接种相同数目并热灭活的Lewis肺癌细胞;PBS组接种等客积的PBS液;空白对照组只做假手术,不注入任何溶液.分别于接种前及接种后第7天起隔日观察小鼠自发痛行为及测定机械触诱发痛.术后第7,15,23天,将小鼠麻醉后行双侧后肢X线摄片,评估肿瘤诱发的骨组织破坏程度.每次摄片后,取小鼠术侧后肢行HE染色,光镜下观察骨质破坏情况.结果:实验组接种后第11天左右出现明显自发痛行为,表现为自发抬足时间延长;接种后第13天左右出现明显的触诱发痛,表现为50%缩足阈值明显下降,且持续整个观察期.术后23 d放射学结果显示,肿瘤细胞充满骨髓腔,且穿破骨皮质向外生长,侵犯周围肌肉组织.结论:C57BL/6小鼠股骨骨髓腔接种Lewis肺癌细胞能够成功制备小鼠骨癌痛模型,且此模型与人类骨癌痛高度相似.

Establishment and evaluation of a bone cancer pain model

OBJECTIVE: To explore the feasibility of a bone cancer pain model by injecting the Lewis lung carcinoma cells into the femur bone marrow cavity of C57BL/6 mice. METHODS: Sixty clear grade male C57BL/6 mice (body weight 18 approximately 20 g) were randomly divided into 4 groups(15 in each group). Cancer cell inoculated group: 2*10(6) Lewis lung carcinoma cells in 10 microL PBS were injected into the left femur bone marrow cavity, and the other 3 control groups were injected the heat inactivated Lewis cells, PBS, or a false operation respectively. Spontaneous lifting time and mechanical allodynia threshold of the mice hind paw were measured in the alternative days throughout the experiment. The structural damage of the femur was monitored by radiogram on the 7th,15th, and 23rd day respectively,and the pathohistological changes of the femur bones were observed by HE staining on the same days. RESULTS: Those mice that received intra-femur innoculation of Lewis lung carcinoma cells gradually developed the spontaneous pain, which was began on the 11th day after the innoculation, and followed by mechanical allodynia. The course of flinch lasted in the later experimental session. The 50% Von Frey threshold was significantly decreased on the 13th day after the innoculation, and the mechanical allodynia lasted the whole experimental period. On the 23rd day after the innoculation, X-ray film showed that the medullary cavity of ipsilateral distal femur was filled with tumor cells, and the cortical bone became thick; furthermore, the tumor cells invaded the peripheral muscles. CONCLUSION: Injecting the Lewis lung carcinoma cells into the femoral medullary cavity of C57BL/6 mice can successfully establish a murine bone cancer pain model, and the murine model shows much resemblance compared with the human bone cancer pain.