Forty-eight male wild-type C57BL/6J mice were obtained at age 6 weeks and separated into 2 groups for diet assignment. After a 1-week acclimation period, half of the mice consumed a high-fat diet (60% fat by kcal) ad libitum to facilitate neuropathic diet-induced obesity whereas the other half were control mice and consumed an age-matched standard low-fat control diet (10% fat by kcal). At age 12 weeks, half of the animals from each group were subjected to a high-intensity inclined treadmill running protocol, which has been previously demonstrated to induce neurotrauma. Sensory testing and radiographic analyses were periodically performed. Histopathologic analyses were performed post killing.
DIO mice had significantly higher bodyweights, higher body fat percentages, and lower bone mineral density than wildtype control mice that were fed a normal diet throughout the experiment (P < .001 for each). DIO mice displayed significantly reduced sensory function in week 1 (P = .005) and this worsened over time, requiring 20.6% more force for paw withdrawal by week 10 (P < .001). DIO mice that ran demonstrated greater midfoot subluxation and tarsal instability over all time points compared with normal-diet mice that ran (P < .001). Histopathologic analyses revealed that DIO mice that ran demonstrated significant changes compared with controls that ran (P < .001 for each parameter).
Changes akin to the earliest changes observed in or before joint destruction identified in diabetic Charcot neuropathic arthropathy in humans were observed.
There is currently no standard of treatment for patients with Charcot neuropathic arthropathy. This study establishes a protocol for an animal model that can be used to study and compare interventions to treat this disease.
■在6周龄时获得48只雄性野生型C57BL/6J小鼠,并分为2组进行饮食分配。经过一周的适应期,一半的小鼠随意摄入高脂肪饮食(60%脂肪,kcal)以促进神经性饮食诱导的肥胖,而另一半是对照小鼠,并摄入年龄匹配的标准低脂肪对照饮食(10%脂肪,kcal).在12周龄时,每组一半的动物接受了高强度倾斜跑步机跑步方案,先前已被证明会引起神经创伤。定期进行感官测试和射线照相分析。杀死后进行组织病理学分析。
■DIO小鼠的体重明显升高,更高的身体脂肪百分比,与在整个实验中饲喂正常饮食的野生型对照小鼠相比,骨矿物质密度较低(每组P<.001)。DIO小鼠在第1周表现出显著降低的感觉功能(P=0.005),并且随着时间的推移而恶化,到第10周时,需要增加20.6%的力量来撤回爪子(P<.001)。与正常饮食的小鼠相比,在所有时间点跑的DIO小鼠表现出更大的中足半脱位和骨不稳定性(P<.001)。组织病理学分析显示,与运行的对照相比,运行的DIO小鼠表现出显著的变化(每个参数P<.001)。
■观察到的变化类似于在人类糖尿病Charcot神经病性关节病中发现的关节破坏中或之前观察到的最早变化。
■目前尚无治疗Charcot神经病性关节病的标准。这项研究建立了一种动物模型的方案,可用于研究和比较治疗这种疾病的干预措施。