阿司匹林联合雷奈酸锶治疗对成骨细胞以及去卵巢大鼠骨密度和骨量的影响

Effect of aspirin combined with strontium ranelate on osteoblasts and bone mineral density and bone mass in ovariectomized rats

目的探讨阿司匹林(aspirin,ASP)联合雷奈酸锶(strontium ranelate,SR)治疗对成骨细胞及去卵巢大鼠骨密度和骨量的影响,并探索可能的机制。方法首先观察ASP、SR以及SR+ASP治疗对MC3T3-E1细胞ALP染色和茜素红染色的影响;然后通过双侧去卵巢建立绝经后骨质疏松症模型;随后去卵巢大鼠随机分为去卵巢组(OVX)、ASP组、SR组以及SR+ASP组;其中ASP组和SR组以及SR+ASP组大鼠分别接受阿司匹林、雷奈酸锶以及两者联合治疗12周;待治疗结束后使用Micro-CT、HE染色切片以及蛋白质印迹观察治疗效果以及可能的机制。结果成骨细胞实验表明,ASP、SR以及SR+ASP均能促进成骨细胞ALP生成以及矿化;而SR+ASP对成骨细胞ALP生成以及矿化最为显著(P<0.05)。治疗12周后,与ASP组和SR组相比,SR+ASP组的大鼠骨小梁数量和骨密度得到明显改善。SR+ASP组大鼠BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较SR组及ASP组明显改善(P<0.05)。和ASP组和SR组比较,SR+ASP组的大鼠Notch信号通路被激活,Notch 1、CBF 1 and Jagged 1水平显著上调,比较差异有统计学意义(P<0.05)。结论SR联合ASP可以改善成骨细胞功能和对去卵巢大鼠骨量保护作用,且这种疗效可能通过Notch信号通路介导。

Objective To investigate the effect of aspirin(ASP)combined with strontium ranelate(SR)on osteoblasts and bone mineral density and bone mass in ovariectomized rats,and to explore the possible mechanism.Methods Firstly,the effect of ASP,SR and SR+ASP on ALP staining and Alizarin red staining of MC3T3-E1 cells were observed.Then the model of postmenopausal osteoporosis was established using bilateral ovariectomy.The ovariectomized rats were randomly divided into OVX group,ASP group,SR group,and SR+ASP group.The rats in ASP group,SR group and SR+ASP group received aspirin,strontium ranelate,or the combination,respectively,for 12 weeks.After the treatment,micro-CT,HE staining,and Western blotting were used to observe the therapeutic effect and possible mechanism.Results Osteoblast experiment showed that ASP,SR,and SR+ASP promoted ALP production and mineralization of osteoblasts.SR+ASP had the most significant effect on ALP production and mineralization of osteoblasts.After 12 weeks of treatment,compared with those in ASP group and SR group,the number of bone trabeculae and bone mineral density in SR+ASP group significantly improved.The levels of BMD,TV/BV,Tb.N,Tb.Th,and Tb.Sp in SR+ASP group were significantly better than those in SR group and ASP group.Compared with that in ASP group and SR group,Notch signal pathway was activated and the levels of Notch-1,CBF-1,and Jagged-1 were significantly up-regulated in SR+ASP group.Conclusion ASP combined with SR can improve the function of osteoblasts and protect bone mass in ovariectomized rats.This effect may be mediated by Notch signal pathway.