格列美脲对高脂饮食ApoE^(-/-)小鼠骨微结构的影响

The effect of Glimepiride on bone microarchitecture in ApoE^(-/-) mice on high fat diet

目的观察格列美脲对高脂饮食喂养的Apo E基因敲除(ApoE^(-/-))小鼠骨微结构的影响。方法以8只野生型C57BL/6小鼠为野生正常组,24只ApoE^(-/-)小鼠随机分为3组,分别为ApoE^(-/-)正常组、ApoE^(-/-)高脂组、格列美脲组。野生正常组和ApoE^(-/-)正常组给予普通饲料饲养,ApoE^(-/-)高脂饮食组和格列美脲组给予高脂饲料,其中格列美脲组小鼠灌服25mg/kg格列美脲,其他各组小鼠均灌服等量去离子水。6w后,处死小鼠,取双侧股骨,分别进行H&E染色和Safrain O/Fast Green染色评价骨微结构,利用骨生物力学评价骨强度,利用Cathepsin K表达评价骨吸收程度。结果格列美脲可明显改善高脂饮食喂养的ApoE^(-/-)小鼠骨微结构,提升股骨糖胺聚糖含量,提高股骨第一循环硬度、峰值压力和硬度形变量,降低Cathepsin K表达。结论格列美脲可改善高脂饮食饲养的ApoE^(-/-)小鼠的骨微结构,其作用机理可能与抑制Cathepsin K的表达相关。

Objective To observe the effect of glimepiride on bone microarchitecture in Apo E knocked out（ Apo-（E-/-）） mice on high fat diet. Methods 8 wild type C57BL/6 mice were recruited as the wild type normal group（ WTN）,24 Apo-（E-/-）mice were randomly divided into three groups： Normal control group（ NC）,High fat diet group（ HFD）,and Glimepiride group（ GP）.The mice in WTN and NC were given normal feed,and the mice in HFD and GP were fed with high fat diet. The mice in GP were given glimepiride（ 25 mg/kg,i. g.）,other mice received the same volume of deionized water. After 6 weeks of administration,all mice were anesthetized and killed. Then the bilateral femurs were harvested. Bone strength of the femurs and microarchitecture were evaluated by bone biomechanics examination, and the staining of HE and safranin O/fast green. Immunohistochemistry staining was used to analyze the expression of Cathepsin K in mice femurs by immunohistochemistry staining. Results Glimepiride treatment significantly improved bone microarchitecture,increased femoral glycosaminoglycan content,and improved the hardness of the first cycle,peak pressure and hardness deformation of mice femurs,as well as decreased the expression of Cathepsin K in Apo-（E-/-）mice on HFD. Conclusion Changes of bone microarchitecture in Apo-（E-/-）mice induced by high fat diet were improved by glimepiride. The mechanism may be related to the inhibition of Cathepsin K expression.