阿魏酸治疗对去卵巢雌性大鼠骨量流失的保护作用机制研究

Study on the protective mechanism of ferulic acid treatment on the bone loss in ovariectomized female rats

目的研究阿魏酸(ferulic acid)对去卵巢大鼠骨量流失的影响,并探讨可能的机制。方法通过双侧去卵巢建立骨质疏松大鼠模型;随后随机分为假手术组(Sham)、去卵巢组(OVX)以及阿魏酸组,每组10只;其中阿魏酸组大鼠每天给予阿魏酸(20 mg/kg)灌胃治疗;待12周治疗结束后使用Micro-CT、HE染色切片、骨代谢指标、骨生物力学检测以及蛋白质印迹观察治疗效果以及探讨可能的机制。结果治疗12周后,与OVX组相比,Micro-CT和HE染色切片结果显示阿魏酸组的大鼠骨小梁数量和骨密度(bone mineral density,BMD)得到明显改善。阿魏酸组大鼠BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较OVX组明显改善(P<0.05)。治疗12周时,阿魏酸组极限载荷和刚度较OVX组显著增加(P<0.05),而阿魏酸组骨代谢指标P1NP和TRACP-5b水平显著降低(P<0.05),比较差异有统计学意义(P<0.05)。和OVX组比较,阿魏酸组BMP-2、Smad1、Smad4、p-Smad1/5/8表达水平上调,比较差异有统计学意义(P<0.05)。结论阿魏酸可以通过BMP2/Smads信号通路抑制去卵巢大鼠的骨量流失。

Objective To explore the effect of Ferulic acid on bone loss in ovariectomized rats and explore the possible mechanisms.Methods In this study,osteoporosis rat models were established by bilateral ovariectomy;they were then randomly divided into sham operation group(Sham),ovary removal group(OVX),and Ferulic acid group,10 in each group;of which burdock Rats in Ferulic acid group received Ferulic acid[20 mg/(kg·day)]for 12 weeks;after treatment,Micro-CT,HE stained sections,bone metabolism indicators,bone biomechanical testing and Western blot were used to observe the treatment effect and possible mechanism.Results After 12 weeks of treatment,compared with the OVX group,the result of Micro-CT and HE staining showed that the number of trabeculae and bone mineral density of the rats in the Ferulic acid group were significantly improved.BMD,TV/BV,Tb.N,Tb.Th,and Tb.Sp in the Ferulic acid group were significantly improved compared with the OVX group(P<0.05).At 12 weeks of treatment,the limit load and stiffness of the Ferulic acid group were significantly increased compared with the OVX group(P<0.05),while the levels of bone metabolism indicators P1NP and TRACP-5b in the Ferulic acid group were significantly reduced(P<0.05),which was statistically significant(P<0.05).Compared with the OVX group,the expression levels of BMP-2,Smad1,Smad4,and p-Smad1/5/8 in the Ferulic acid group were up-regulated,and there was a statistical difference(P<0.05).Conclusion Ferulic acid mediates the protective effect on bone loss in ovariectomized rats through the BMP2/Smads signaling pathway.