依折麦布对高脂饮食ApoE-/-小鼠骨微结构的影响

摘要

目的 观察依折麦布对高脂饲料喂养的ApoE基因敲除(ApoE-/-)小鼠骨微结构的影响.方法 选取8只野生型C57 BL6小鼠为野生正常组,将24只ApoE-/-小鼠随机分为ApoE-/-正常组、ApoE-/-高脂组、ApoE-/-高脂加依折麦布组(依折麦布组).其中依折麦布组小鼠给予依折麦布10 mg/(kg·d)灌胃,其他各组小鼠给予等量去离子水灌胃.6周后取各组小鼠的股骨,分别利用HE染色和番红O/固绿染色观察骨微结构,利用质构仪测定骨生物力学,用免疫组化法测定Cathepsin K蛋白表达情况.结果 依折麦布组小鼠骨微结构均明显改善,股骨的第一循环硬度和峰值压力均明显高于ApoE-/-高脂组(P均＜0.05),股骨Cathepsin K蛋白表达量均明显低于ApoE-/-正常组和ApoE--高脂组(P均＜0.05).结论 依折麦布能明显改善高脂饲料喂养的ApoE-/-小鼠骨微结构,提高骨强度,其作用机制与降低Cathep-sin K表达量有关.%Objective It is to observe effect of Ezetimibe on bone microstructure in ApoE gene knockout (ApoE-/-) mice fed with high fat diet.Methods 8 wild type C57BL6 mice were recruited as the wild type normal group,24 ApoE-/-mice were randomly divided into 3 groups:ApoE-/-normal group,ApoE-/-high fat group,ApoE-/-high fat plus Ezetimibe group (Ezetimibe group).The mice in Ezetimibe group were given Ezetimibe (10 mg/kg/day) by gavage,the mice in the other groups were given the same volume of deionized water.After 6 weeks,the femur and tibia of mice were taken to observe bone microstructure by staining of HE and Safrain O/FastGreen,and to measure biomechanics by a texture analyzer.The expression of Cathepsin K was determined by immunohistochemistry.Results The bone microstructure in Ezetimibe group was significantly improved,the hardness of the first cycle of mice femur and peak pressure were significantly higher than those in ApoE-/-high fat group (P ＜ 0.05),the expression of Cathepsin K in femur was significantly lower than that in ApoE-/-normal group and ApoE-/-high fat group (P ＜0.05).Conclusion Ezetimibe can obviously improve bone microstructure,increase bone strength in ApoE-/-mice fed with high fat diet,the underlying mechanism may be related to the reduction of Cathepsin K activity.