阿魏酸对阿尔兹海默症模型小鼠骨骼的影响

Effects of ferulic acid on bone in Alzheimer's disease model mice

目的探究阿魏酸对阿尔兹海默症模型小鼠骨量和骨结构的影响。方法5只6月龄雄性C57BL/6J小鼠作为野生型(WT)组,20只6月龄雄性转基因APP/PS1(C57BL/6J)小鼠随机分为模型对照(MC)组、生理盐水(NS)组、阿魏酸低剂量(FA-L,30 mg/kg)组与阿魏酸高剂量(FA-H,60 mg/kg)组,每组5只,给药6个月。实验结束前进行小鼠筑巢实验与旷场迷宫实验,实验结束后处死小鼠并分取血清,ELISA法检测血清中ALP和TRACP-5b水平,分取胫骨,经脱钙后以石蜡包埋并切片,HE染色后采用骨形态计量学分析骨量和骨结构。结果与WT组相比,MC组小鼠的筑巢评分显著下降(P<0.01),旷场迷宫实验总路程、中央区域路程、中央区域时间和平均速度均显著降低(P<0.05),血清ALP无明显变化,但TRACP-5b显著升高(P<0.05),骨小梁面积百分数、骨小梁宽度、骨小梁数量显著减少(P<0.05),骨小梁分离度显著增加(P<0.05),皮质骨面积百分比与皮质骨厚度显著减少(P<0.01),骨髓腔面积百分比显著增加(P<0.01);与MC组相比,NS组各项指标无明显变化;与NS组相比,FA-L和FA-H组小鼠筑巢评分显著升高(P<0.05),旷场迷宫实验总路程、中央区域路程、中央区域时间和平均速度均显著升高(P<0.01),血清ALP无明显变化,但TRACP-5b显著降低(P<0.01),骨小梁面积百分数、骨小梁宽度、骨小梁数量显著增加(P<0.05),骨小梁分离度显著减小(P<0.05),皮质骨面积百分比与皮质骨厚度显著增加(P<0.05),骨髓腔面积百分比显著减小(P<0.01)。结论阿魏酸干预有效减缓了阿尔兹海默症模型小鼠胫骨的骨量丢失,并改善了骨结构。

Objective To investigate the effect of ferulic acid on bone mass and bone structure of Alzheimer's disease model mice.Methods Five 6-month-old C57BL/6J male mice were used as the wild type(WT)group,and twenty 6-month-old male APP/PS1 transgenic mice were randomly divided into model control(MC)group,normal saline(NS)group,low-dose ferulic acid(FA-L,30 mg/kg)group,and high-dose ferulic acid(FA-H,60 mg/kg)group,with 5 mice in each group.The experiment lasted for 6 months.Nesting test and open field maze test were performed to evaluate the cognitive ability and emotional changes of the mice before the animals were sacrificed.After the Nesting test and open field maze test,mice were euthanized.Serum was collected to detect ALP and TRACP-5b levels with ELISA.Samples of the tibia were decalcified and fixed,paraffin-embedded,sectioned,and stained with HE for bone histomorphometry.Results Compared to those in WT group,nesting score in the MC group decreased significantly(P<0.01).Total distance,central area distance,central area time,and average speed decreased remarkably(P<0.05).There was no significant change in serum ALP level,but TRACP-5b increased remarkably(P<0.05).Percentage of trabecular bone area,trabecular bone width,and trabecular bone number decreased significantly(P<0.05).Separation of trabecular bone increased remarkably(P<0.05).Percentage of cortical bone area and cortical bone thickness decreased significantly(P<0.01).Percentage of marrow cavity area increased remarkably(P<0.01).Compared with MC group,there were no significant changes in all parameters in NS group.Compared to those in NS group,Nesting score(P<0.05),total distance,distance in central area,and time and the average speed in central area(P<0.01)significant increased in FA-L and FA-H groups.Serum ALP did not change significantly,but TRACP-5b remarkably decreased(P<0.01).Percentage of trabecular bone area,trabecular bone width,and trabecular bone number increased significantly(P<0.05).Separation of trabecular bone decreased remarkably(P<0.05).Percentage of cortical bone area and cortical bone thickness increased significantly(P<0.05).Percentage of marrow cavity area decreased remarkably(P<0.01).Conclusion Ferulic acid prevents bone loss and improves bone structure in the tibia of AD model mice.