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骨质疏松性骨折的小鼠模型探索
李伟龙, 余霄, 毛宾尧, 庞清江
宁波大学医学院
摘要:
目的建立操作简单、重复性好的骨质疏松性骨折小鼠动物模型,以用于中老年女性绝经后骨质疏松性骨折愈合情况的研究。方法选取12周龄健康的C57BL/6J雌性小鼠50只,其中基线组10只,去势组20只,假手术组20只。常规饲养1周后,处死基线组小鼠并测量血清雌激素水平,去势组小鼠通过腹正中切口行双侧卵巢切除,假手术组小鼠切除双侧卵巢周围等量的脂肪组织。去势后4周对小鼠的左大腿行后外侧切口,暴露股骨,从膝关节处逆行插入钢针进行髓内固定,直视下用手术刀切断股骨中下1/3段部分,造成股骨的横行或斜行骨折。两组小鼠在骨折术后2周和4周分别处死10只,测量血清雌激素水平、骨痂处骨密度(BMD)及Micro-CT情况。结果术后2周和4周假手术组雌激素浓度均高于去势组,差异均有统计学意义(均P<0.05)。术后2周和4周假手术组和去势组BMD、骨体积、骨体积分数比较,差异均有统计学意义(均P<0.05)。虽然术后2周假手术组和去势组骨小梁分离度(Tb.Sp)比较差异无统计学意义(P>0.05),但术后4周两组Tb.Sp比较差异有统计学意义(P<0.05),而术后2周和4周两组骨小梁结构模型指数比较差异均无统计学意义(均P>0.05)。结论小鼠骨质疏松性骨折模型具有操作简单、直观稳定等优点;去势后的小鼠成骨能力明显下降,可用于原发性绝经后骨质疏松性骨折的愈合及其骨代谢的细胞、分子及信号通路的机制研究。
关键词:  雌性小鼠 去势 骨质疏松性骨折 动物模型
DOI:10.12056/j.issn.1006-2785.2017.39.16.2016-1676
分类号:
基金项目:浙江省医药卫生科技计划重点项目(2015ZDA026)
Establishment of a mouse osteoporotic fracture model
LI Weilong, YU Xiao, MAO Binyao, PAN Qingjiang
Ningbo University School of Medicine
Abstract:
Objective To establish a simple and reproducible osteoporotic fracture model in mice. Methods Fifty 12-week C57BL/6J female mice were randomly divided into control group (n=10), sham group (n=20) and model group (n=20). Mice in control group were sacrificed after one week and the serum estrogen levels were measured. Mice in model group underwent bilateral ovariectomy, while sham operation was given to mice in sham group. One month after operation, the left femur was exposed by lateral incision on left thigh of mice, intramedulary nailing was performed from knee joint for internal fixation, the lower middle 1/3 section of the femur was severed under direct vision to make a transverse or short oblique fracture of the femur. At the week 2 and 4 after operation, the mice in both groups were sacrificed in batches (n=10 for each), serum estrogen levels were measured, bone mineral density (BMD) was determined and the callus were examined with Micro-CT. Results The serum estrogen levels in model group were lower than those in sham group at week 2 and 4 after operation (both P<0.05). There were significant differences in BMD, bone volume and relative volume fraction between sham group and model group at week 2 and 4 after operation (all P<0.05). Trabecula separation was significantly higher in model group than that in sham group at week 4 after surgery (P<0.05), while there was no significant difference in week 2 (P >0.05). There was no significant difference in structure model index between the two groups (P >0.05). Conclusion Ovariectomy and intramedullary nailing is a simple, intuitional and stable method for establishing a open osteoporotic femur fracture model in mice, which may be used in laboratory study for post- menopausal osteoporotic fracture and bone metabolism.
Key words:  Female mice Ovariectomy Osteoporotic fracture Animal model