基于Nrf2与NF-κB通路及交互串话研究广西黑蚁活性组分抑制破骨细胞防治骨质疏松症的作用机制

破骨细胞参与骨质疏松发生、发展，其活化与ROS氧化应激介导Nrf2与NF-κB通路及交互串话密切相关。项目组前期研究发现：广西黑蚁活性组分（AFPR）可干预破骨细胞从而抑制骨质疏松小鼠骨量丢失；AFPR可降低小鼠体内过氧化氢含量，提高抗氧化因子活性，提示AFPR抗骨质疏松作用与ROS氧化应激活化破骨细胞有关；同时，AFPR可抑制破骨细胞分化并下调破骨细胞中NF-κB水平，但对细胞核内Nrf2表达呈现促进趋势，提示AFPR干预破骨细胞活化可能与ROS氧化应激介导Nrf2与NF-κB通路及交互串话有关。本项目拟在此基础上，从细胞水平明确广西黑蚁活性组分对ROS氧化应激活化破骨细胞的具体作用；从分子水平深入解析其对ROS氧化应激活化破骨细胞介导的Nrf2与NF-κB及交互串话调控作用及机理；最后从动物水平全面阐明其对骨质疏松的作用及调节机制，以期为骨质疏松的临床治疗提供理论和实验依据。

Osteoclast plays an important role in the development and progression of osteoporosis. The Nrf2 and NF-κB signaling pathways and the molecular cross-talk between Nrf2 and NF-κB response pathways mediated by oxidative stress (OS) are closely related to the activation of osteoclast. Our previous studies showed that Active Fraction from Polyrhachis vicina Roger (AFPR) could protect from OVX-induced bone loss via suppressing osteoclast. We also discovered that AFPR could attenuate the serum levels of H2O2 and improve activities of antioxidant factors, indicating the anti-osteoporosis of AFPR may be related to the OS-induced activation of osteoclast. Further preliminary studies found that AFPR could suppress osteoclastogenesis. In addition, our studies showed that AFPR could suppress the transcript levels of NF-κB, and also prompt the levels of nuclear Nrf2 during the osteoclastogenesis. These findings indicated that inhibition of osteoclast activation by AFPR may be ascribed to the regulation of the Nrf2 and NF-κB signaling pathways and the molecular cross-talk between Nrf2 and NF-κB response pathways. Based on the previous studies, firstly, experiments in vitro will be performed to demonstrate the effect of AFPR on OS-stimulated osteoclast. Secondly, we further at the molecular level investigate that the action and regulatory mechanism of AFPR on the OS mediated Nrf2 and NF-κB signaling pathways and the molecular cross-talk between Nrf2 and NF-κB response pathways. Finally, the effect and regulatory mechanism of AFPR on OVX-mice model will be examined. This study will provide a novel strategy for the treatment of osteoporosis in the future.