麦角甾苷治疗对去卵巢大鼠骨质疏松症保护机制研究

Protective mechanism of ergosteroid glycoside treatment for osteoporosis in ovariectomized rats

目的探讨麦角甾苷(MJZG)治疗对去卵巢大鼠骨密度降低和骨量流失的潜在影响,并探索可能的机制。方法通过双侧去卵巢构建骨质疏松大鼠模型;随后将大鼠随机分为假手术组(Sham)、去卵巢组(OVX)以及麦角甾苷(MJZG),每组10只;其中MJZG组大鼠接受麦角甾苷(100 mg/kg)治疗12周;待治疗截止时获取股骨标本和血液样品进一步检测股骨骨量、骨强度、骨代谢指标改变以及组织蛋白的表达。结果术后12周,与Sham组相比,OVX组的大鼠骨小梁微观参数和骨密度和骨矿物质含量以及骨强度显著降低;而MJZG组大鼠BMD、BV/TV、Tb.N、Tb.Th和Tb.Sp以及最大载荷和弹性模量较OVX组明显改善(P<0.05)。MJZG组大鼠血清BGP、ALP、TRACP-5b和DPD水平较OVX组明显降低,组间差异有统计学意义(P<0.05)。WB检测观察到,和OVX组比较,MJZG组的TRAF6、RANKL、NF-κB和NFAT2的蛋白水平表达下调(P<0.05),而PI3K、AKT和c-Fos上调(P<0.05)。结论MJZG可以通过抑制RANKL/TRAF6/NF-κB和激活PI3K/AKT防治去卵巢诱导的骨质疏松症。

Objective To explore the potential effect of ergosteroid glycoside(MJZG)treatment on the reduction of bone mineral density and bone loss in ovariectomized rats,and to explore the possible mechanism.Methods A rat model of osteoporosis was constructed with bilateral ovariectomy.The rats were then randomly divided into sham operation group(Sham),ovariectomized group(OVX),and MJZG group,with 10 rats in each group.The rats in MJZG group received MJZG(100 mg/kg)treatment for 12 weeks.The femoral specimens and blood samples were obtained at the end of the treatment to further detect femoral bone mass,bone strength,changes in bone metabolism indexes,and tissue protein expression.Results After 12 weeks of the operation,trabecular bone micro-parameters,bone mineral density,bone mineral content,and bone strength in OVX group reduced significantly compared to those in Sham group.BMD,BV/TV,Tb in MJZG group,N,Tb.Th,Tb.Sp and the maximum load and elastic modulus improved significantly compared to those in OVX group(P<0.05).The serum levels of BGP,ALP,TRACP-5b,and DPD of rats in MJZG group were significantly lower than those in OVX group,and the difference between the two groups was statistically significant(P<0.05).The protein levels of TRAF6,RANKL,NF-κB,and NFAT2 were down-regulated(P<0.05),while PI3K,AKT,and c-Fos were up-regulated(P<0.05)in MJZG group compared to those in OVX group with WB detection.Conclusion MJZG prevents and treats osteoporosis induced by ovariectomy by inhibiting RANKL/TRAF6/NF-κB and activating PI3K/AKT.