仙茅酚苷类成分介导p62整合调控Nrf2/自噬/NF-κB通路抑制氧化应激诱导的破骨细胞形成分化的机制研究

雌激素缺失及其导致的氧化应激增加是骨质疏松症发生的关键因素。抗衰老中药仙茅具有调节免疫、抗氧化和抗骨质疏松等作用，常用于防治骨质疏松的中药方剂中。前期研究发现仙茅酚苷类成分能够减少去卵巢和氧化应激诱导的骨丢失，抑制破骨细胞的形成分化，其机制可能与其介导p62对抗氧化应激、抑制自噬和破骨细胞形成分化有关。本课题拟研究仙茅酚苷类成分对去卵巢联合铁超载诱导的氧化应激致骨质疏松小鼠抗氧化体系、自噬和骨代谢的调控作用；研究其介导p62整合调控RANKL和H2O2诱导的破骨细胞Nrf2、自噬和NF-κB通路的机制，及其调控Nrf2、自噬和NF-κB通路的关联性，阐明仙茅酚苷类成分抑制氧化应激诱导破骨细胞形成分化的机制，揭示抗衰老中药仙茅防治骨质疏松症的科学内涵，也将为仙茅酚苷类成分作为p62抑制剂用于氧化应激和破骨细胞性骨吸收增强导致骨丢失的相关疾病治疗提供科学的依据。

Estrogen deficiency and its inducible elevation in oxidative stress are key factor for osteoporosis. Curculigins rhizoma, an important anti-aging traditional Chinese medicine, has the action of immunomodulation, antioxidation and antiosteoporosis, and are often used in the traditional Chinese medicine formula for prevention and treatment for osteoporosis. Our previous investigation showed that phenolic glucosides from Curculigins rhizoma attenuated the bone loss induced by ovariectomy and oxidative stress, and inhibited the osteclastogenensis. This effects may be related with these constituents mediating p62 to counteract oxidative stress and inhibit autophagy and regulate the formation and differentiation of osteoclast. In this project, we will investigate the regulatory effects of phenolic glucosides from Curculigins rhizoma on oxidative stress, autophagy and bone metabolism in oxidative osteoporotic mice induced by combination of overactomy with iron overload, explore the regulatory mechanism of phenolic glucosides from Curculigins rhizoma on Nrf2, autophagy and NF-κB pathway in osteoclast induced from RAW264.7 with RANKL and H2O2, and and analyze the correlation of regulatory effects of phenolic glucosides from Curculigins rhizoma on Nrf2, autophagy and NF-κB pathway, finally elucidate the scientific connotation of prevention and treatment osteoporosis of antiaging traditional Chinese medicine Curculigins rhizoma, and also provide scientific basis for phenolic glucosides from Curculigins rhizoma as p62 inhibitor to treat disease related with bone loss induced by oxidative stress and excessive osteoclastic bone resorption.