水飞蓟宾通过PI3K/AKT/FoxO1通路改善骨质疏松大鼠骨代谢和骨量

Silibinin improves bone metabolism and bone mass in osteoporosis rats through PI3K/AKT/FoxO1 pathway

目的探讨水飞蓟宾对糖皮质激素性骨质疏松(GIOP)大鼠骨量影响以及对PI3K/AKT/FoxO1通路影响。方法将30只12周龄雄性Sprague Dawley大鼠随机分为3组:对照组(n=10);地塞米松组(n=10)及地塞米松+水飞蓟宾组(n=10),对应给予地塞米松及水飞蓟宾治疗。12周后取双侧股骨进行微型计算机断层扫描(Micro-CT)和骨生物力学检测。同时检测抗酒石酸酸性磷酸酶(TRACP)、Ⅰ型胶原交联羧基末端肽(CTX-I)、碱性磷酸酶(ALP)和骨钙素(OC)。蛋白印迹分析大蒜素对PI3K/AKT/FoxO1通路影响。结果地塞米松组大鼠的骨密度(BMD)、骨微观结构和骨生物力学指标均明显低于对照组(P<0.05)。骨吸收指标(TRACP和CTX-I)升高,骨形成指标(ALP和OC)降低。水飞蓟宾治疗后骨密度、骨微观结构、骨生物力学指标均有明显改善。与地塞米松组相比,地塞米松+水飞蓟宾组的TRACP和CTX-I显著降低,ALP和OC显著升高。进一步研究表明水飞蓟宾可以通过抑制地塞米松介导PI3K/AKT/FoxO1信号通路上调来调控骨代谢。结论水飞蓟宾可以通过PI3K/AKT/FoxO1信号通路调控骨代谢,提高GIOP大鼠骨密度、骨微观结构和骨强度。

Objective To investigate the effects of Silibinin on the bone mass of rat models with glucocorticoid-induced osteoporosis(GIOP).Methods Thirty male Sprague Dawley rats aged 12 weeks were randomly divided into three groups:the control group(n=10)was intramuscularly injected with an equal volume of 0.9%sodium chloride;the dexamethasone group(n=10)was intramuscularly injected with dexamethasone at 1 mg/kg(twice a week)to induce GIOP;the dexamethasone plus Garlic extract group(n=10)was subcutaneously gavaged with Silibinin,simultaneously.The bilateral femurs were collected after 12 weeks to perform micro-computed tomography and bone biomechanical examinations.Also,tartrate-resistant acid phosphatase(TRACP),cross-linked carboxy-terminal telopeptide of type I collagen(CTX-I),alkaline phosphatase(ALP),and osteocalcin(OC)were tested.Western blot analysis of the effect of allicin on PI3K/AKT/FoxO1 pathway.Results The bone mineral density(BMD),bone microstructure,and bone biomechanical markers reduced significantly in the dexamethasone group compared with the control group(P<0.05).The bone resorption indicators(TRACP and CTX-I)increased,while the bone formation indicators(ALP and OC)decreased.After Silibinin treatment,BMD,bone microstructure,and bone biomechanical markers improved significantly.Moreover,TRACP and CTX-I decreased significantly,while ALP and OC increased compared with the dexamethasone group.Further studies have shown that Silibinin can regulate bone metabolism by inhibiting dexamethasone-mediated up-regulation of PI3K/AKT/FoxO1 signaling pathway.Conclusion Silibinin can regulate bone metabolism through PI3K/AKT/FoxO1 signaling pathway,and improve bone mineral density,bone microstructure and bone strength in GIOP rats.