高浓度骨桥蛋白诱导双足直立雌性小鼠脊柱侧凸模型

A scoliosis model of bipedal female mouse induced by high-concentration osteopontin

背景:近年来相关研究证实骨桥蛋白水平增高可能导致特发性脊柱侧凸发生发展。建立合适的青少年特发性脊柱侧凸动物模型对于此类疾病的研究与治疗具有重大意义。目的:观察高浓度骨桥蛋白诱导双足直立雌性小鼠脊柱侧凸的发生情况,为建立理想的青少年特发性脊柱侧凸药物模型提供依据。方法:选取同周龄C3H/HeJ小鼠,随机分为高浓度骨桥蛋白雌性小鼠及雄性小鼠各20只,并设立对照雄性小鼠组及对照雌性小鼠组各20只。4组小鼠均于3周龄施行上肢截肢合并鼠尾切除术建立双足直立小鼠模型,术后放置特殊鼠笼诱导直立状态。高浓度骨桥蛋白雌性小鼠组及高浓度骨桥蛋白雄性小鼠组每日腹腔注射高浓度(40μg/kg)骨桥蛋白,对照组腹腔注射生理盐水,诱导3个月后,行小动物脊柱X射线检查,测量Cobb角大于10°定为侧凸诱导成功,评估侧凸发生率及严重程度。结果与结论:(1)高浓度骨桥蛋白雌性小鼠组18只发生脊柱侧凸,Cobb角16°-38°,平均(25.8±6.7)°,高浓度骨桥蛋白雄性小鼠组16只发生脊柱侧凸,Cobb角11°-34°,平均(20.9±6.8)°;对照雄性小鼠组8只发生脊柱侧凸,Cobb角12°-21°,平均(15.6±3.1)°;对照雌性小鼠组9只发生脊柱侧凸,Cobb角11°-24°,平均(17.1±4.5)°;(2)高浓度骨桥蛋白雌性、雄性小鼠组脊柱侧凸发生率均明显高于对照雌性、雄性小鼠组(P<0.05),而脊柱侧凸发生率在高浓度骨桥蛋白雌性组与雄性组间差异无显著性意义(P>0.05),但其侧凸角度高浓度骨桥蛋白雌性组较高浓度骨桥蛋白雄性组明显加重(P<0.05);(3)结果表明,高浓度骨桥蛋白水平诱导的雌性双足直立小鼠其侧凸发生率更高,侧凸严重程度更重,其更贴近于人类特发性脊柱侧凸女性高发的实际情况。

BACKGROUND： In recent years, the relevant research confirmed that increased levels of osteopontin may lead to the development of adolescent idiopathic scoliosis. The establishment of appropriate animal models of adolescent idiopathic scoliosis is of great significance in the research and treatment of such diseases. OBJECTIVE： To observe the occurrence of scoliosis of the bipedal female mice induced by high concentration of osteopontin, and provide evidence for establishing ideal drug models of adolescent idiopathic scoliosis. METHODS： C3H/He J mice of the same age were selected and randomly assigned to high-concentration osteopontin female mice（n=20） and male mice（n=20）. This study also set control male mice group（n=20） and control female mice group（n=20）. Mice aged 3 weeks from four groups were subjected to upper limb amputation and rat tail resection to establish bipedal mouse models. After surgery, a special cage was used to induce the upright state. High-concentration osteopontin female mice and male mice were daily intraperitoneally injected with high-concentration osteopontin（40 μg/kg）. Mice in the control group were intraperitoneally injected with physiological saline. At 3 months after induction, animal spine X-ray examination was conducted to measure Cobb angle. If Cobb angle was greater than 10°, a successful induction was set. The incidence and severity of scoliosis were evaluated. RESULTS AND CONCLUSION：（1） In the high-concentration osteopontin female mice group, scoliosis was observed in 18 mice. Cobb angle was 16°-38°, averagely（25.8±6.7）°. In the high-concentration osteopontin male mice group, scoliosis was observed in 16 mice. Cobb angle was 11°-34°, averagely（20.9±6.8）°. In the control male mice group, scoliosis was observed in 8 mice. Cobb angle was 12°-21°, averagely（15.6±3.1）°. In the control female mice group, scoliosis was observed in 9 mice. Cobb angle was 11°-24°, averagely（17.1±4.5）°.（2） The incidence of scoliosis was significantly higher in the high-concentration osteopontin female and male mice groups than in the control female and male mice groups（P 〈0.05）. No significant difference in the incidence of scoliosis was detected between high-concentration osteopontin female and male mice groups（P 〈0.05）. However, curve magnitude was significantly severer in the high-concentration osteopontin female mice group than in the high-concentration osteopontin male mice group（P 〈0.05）.（3） Results suggested that the scoliosis incidence was higher and scoliosis was severer in high-concentration osteopontin-induced bipedal mice, which was more closed to human.