骨质疏松是COPD常见的并发症，其具体的致病机制仍不清楚。我们前期研究提出骨髓脂质代谢失衡是骨衰败的重要病理基础，近期部分细胞分子水平上的研究证实氧化应激能够在一定程度上促进骨髓脂肪形成，且这种作用可能是通过启动PPARϒ2转录调节机制促进骨髓间充质干细胞的成脂分化来实现的。然而细胞的生存环境有异于活体状态，在分子水平所得的研究结论仍需要得到活体水平研究结果的支持。据此我们提出科学假说，COPD可能存在骨髓脂肪异常浸润，且氧化应激可能是COPD骨髓脂代谢失衡的重要因素，并通过上调PPARϒ2的表达介导COPD骨髓脂肪增多，进而引起COPD骨质衰败。因此，本研究拟利用MRI水/脂分离技术首先探讨COPD患者腰椎骨髓脂肪含量变化，初步分析骨髓脂肪与氧化应激、骨代谢之间的关系；并通过活体动物实验进一步研究PPARϒ2在氧化应激介导的COPD骨髓脂肪增多中的作用。

Oxidative stress is a hallmark of COPD. Osteoporosis is one of the most complicatioms of COPD, which may directly be attributable to the Oxidative stress,however the specific mechanism is still unclear. There is growing interest in the relationships between bone and bone marrow. Our previous studies suggest that metabolic abnormalities of marrow fat play vital roles on bone deterioration. At a cellular level,several ex vivo studies have revealed that oxidative stress could enhance marrow adipogenesis, which may be attributable to the transcriptional activation of peroxisome proliferator-activated receptor gamma (PPARγ2) to modulate the differentiation of bone marrow derived mesenchymal stem cells. However, the living environment of cells is significantly different from that of in vivo status. Based on the above analyses, We hypothesize that 1) fatty marrow infiltration may occur in COPD patients; 2) oxidative stress may be one of the most important factors for marrow adipogenesis in COPD; and 3) upregulation of PPARγ2 may be involved in the development of marrow adiposity in COPD,which in turn leads to bone deterioration of COPD. To test these hypotheses, we used water-fat separation MRI technique to detect the changes of vertebral marrow fat content in COPD patients, and analyzed the relationships of marrow fat content.with oxidative stress and bone turnover biomarkers. Further, we elucidated the roles of PPARγ2 on the marrow adipogenesis of oxidative stress mediated COPD in a rat model of COPD and ovariectomy-induced osteoporosis .