基于STING/NF-κB信号通路探讨茯苓酸对去卵巢小鼠骨质疏松的作用

Effect of pachymoic acid on osteoporosis in ovariectomized mice based on STING/NF-κB signaling pathway

目的评价茯苓酸通过调控STING/NF-κB信号通路对去卵巢小鼠骨质疏松的影响。方法取40只SPF级雌性C57BL/6小鼠随机分为假手术组(Sham)、模型组(OVX)、17β-雌二醇组(E_(2),10µg/kg)和茯苓酸组(FL,5 mg/kg),通过切除双侧卵巢建立小鼠骨质疏松模型。8周实验结束后分别检测血清碱性磷酸酶(ALP)和抗酒石酸酸性磷酸酶(StrACP)水平,观察股骨远端形态学和胫骨(皮质骨)骨形成动态变化,测定右侧股骨的生物力学和STING/NFκB通路关键蛋白表达水平。结果与OVX组比较,E2组和FL组小鼠血清StrACP和ALP水平明显降低(P<0.01),股骨远端骨小梁面积百分数明显增加(P<0.01),皮质骨双荧光间距明显减少(P<0.01),股骨最大载荷和断裂载荷明显升高(P<0.01),股骨STING和p-NF-κB p65/NF-κB p65蛋白表达水平明显降低(P<0.01)。结论茯苓酸通过调控STING/NF-κB信号通路抑制骨吸收和促进骨形成,从而有效减少去卵巢小鼠骨丢失。

Objective To evaluate the effect of pachymoic acid on osteoporosis in ovariectomized mice by regulating STINGNF-κB signaling pathway.Methods Forty SPF female C57BL/6 mice were divided into sham operation group(Sham),model group(OVX),17β-estradiol group(E_(2),10µg/kg)and pachymoic acid group(FL,5 mg/kg),and the osteoporosis model of mice was established by bilateral ovariectomy.After 8 weeks,the levels of serum alkaline phosphatase(ALP)and tartrate-resistant acid phosphatase(StrACP)were detected,the morphology of distal femur and the dynamic changes of tibia(cortical bone)bone formation were observed,and the biomechanics of the right femur and the expression levels of key proteins in STING/NF-κB pathway were determined.Results Compared with OVX group,the levels of serum StrACP and ALP in E2 group and FL group were significantly lowered(P<0.01),the area percentage of trabecular bone in distal femur was increased(P<0.01),and the double-fluorescence distance between cortical bones was decreased(P<0.01).The maximum load and fracture load of femur were significantly elevated(P<0.01),and the expression levels of STING and p-NF-κB p65/NF-κB p65 protein in femur were significantly increased(P<0.01).Conclusion Pachymoic acid can inhibit bone resorption and promote bone formation by regulating STING/NF-κB signaling pathway,thereby effectively reducing bone loss in ovariectomized mice.