PM2.5暴露对绝经后骨质疏松症的影响及其机制的实验研究

Postmenopausal osteoporosis (PMOP) is a systemic bone disease caused by estrogen deficiency, which is characterized by serious complications including bone fracture and high morbidity among middle-aged women. Particulate matters (PM2.5) exposure has been shown to be associated with the loss of bone mass and decreased bone mineral density. However, it remains unclear whether PM2.5 is related to the occurrence and progression of PMOP. In the present project, we will establish an artificial menopause model exposed to PM2.5 in female SD rats. Bone mineral density, bone metabolic parameters and sex hormone levels at certain periods before and after the menopause, and changes of the proteins and mRNA expressions of the estrogen receptors and the receptors related to bone metabolism will be investigated. Furthermore, the expressions of estrogen receptors α/β and polycyclic aromatic hydrocarbon receptors and levels of the proteins and mRNAs related to OPG/RANKL/RANK pathway will be observed in the osteoblast/osteoclast culture system and follicle cell culture system challenged by PM2.5 ,respectively. The present study will clarify whether PM2.5 exposure may affect POMP and will uncover its underlying mechanisms via the receptor and inflammatory mediator pathways, providing an additional clue for PMOP prevention and treatment.

绝经后骨质疏松症（PMOP）是由女性雌激素缺乏而引发的全身性骨病，是中老年妇女的高发疾病，由其导致的并发症、致残率均很高。研究显示大气细颗粒物（PM2.5）暴露与骨量丢失、骨密度下降有关，但PM2.5是否参与PMOP的发生及进展，其作用机制如何均不明确。项目在雌性SD大鼠PMOP模型上实施PM2.5暴露，通过骨密度、血清骨代谢指标及性激素水平，以及骨代谢相关受体、雌激素相关受体蛋白及mRNA表达变化，研究PM2.5对PMOP的影响；通过成骨细胞/破骨细胞共培养体系、卵泡细胞共培养体系暴露于PM2.5后，观察ERα、ERβ、AhR 受体，OPG、RANKL、RANK蛋白及其mRNA的表达变化，探讨PM2.5对PMOP的影响机制。本课题将明确不同水平PM2.5暴露对PMOP的影响，阐明PM2.5作用于PMOP的受体途径和炎性介质参与机理，为PMOP防治提供新的线索。

绝经后骨质疏松症（PMOP）是由女性雌激素缺乏而引发的全身性骨病，是中老年妇女的高发疾病，由其导致的并发症、致残率均很高。研究显示大气细颗粒物（PM2.5）暴露与骨量丢失、骨密度下降有关，但PM2.5是否参与PMOP的发生及进展，其作用机制如何均不明确。项目在雌性SD大鼠PMOP模型上实施PM2.5暴露，通过骨密度、血清骨代谢指标及性激素水平，以及骨代谢相关受体、雌激素相关受体蛋白及mRNA表达变化，研究PM2.5对PMOP的影响；通过成骨细胞/破骨细胞共培养体系、卵泡细胞共培养体系暴露于PM2.5后，观察ERα、ERβ、AhR 受体，OPG、RANKL、RANK蛋白及其mRNA的表达变化，探讨PM2.5对PMOP的影响机制。本课题将明确不同水平PM2.5暴露对PMOP的影响，阐明PM2.5作用于PMOP的受体途径和炎性介质参与机理，为PMOP防治提供新的线索。