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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C57BL6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Cathepsin K表达量有关。
Objective To observe the effect of ezetimibe on the microarchitecture of ApoE ~ (- / -) mice fed with high fat diet. Methods Totally 24 wild type ApoE ~ (- / -) mice were randomly divided into ApoE ~ (- / -) normal group, ApoE ~ (- ApoE ~ (- / -) high fat plus ezetimibe group (ezetimibe group). Ezetimibe group mice were given ezetimibe 10 mg / (kg · d) gavage, the other groups of mice given the same amount of deionized water gavage. Six weeks later, the femur of each group was taken and the bone microarchitecture was observed by HE staining and safranin O / green staining respectively. The biomechanics of the bone was measured by the texture analyzer, and the expression of Cathepsin K protein was detected by immunohistochemistry. Results The micro-structure of the ezetimibe group was significantly improved, the first cycle stiffness and peak pressure of the femur were significantly higher than those of the ApoE ~ (- / -) hyperlipidemia group (all P <0.05), and the expression of Cathepsin K protein The levels were significantly lower than those in ApoE ~ (- / -) normal group and ApoE ~ (- / -) high fat group (all P <0.05). Conclusion Ezetimibe can significantly improve the bone microarchitecture and improve the bone strength of ApoE ~ (- / -) mice fed with high fat diet, and its mechanism may be related to the decrease of Cathepsin K expression.