绝经后腰椎骨、腹部脂肪交互作用关系及机制的实验研究

The loss of bone has high morbidity in postmenopausal women and these skeletal diseases severely affect the life quality of patients, which becomes a tremendous and growing public health issue. There may be a close relationship between these skeletal diseases and the change of body adipose tissue redistribution and quantity after menopause. There should be an integrated physiological regulation mechanism exists between bone and adipose tissue interactions in the context of declining of sex hormones secretion. However, the regulation mechanism remains unclear, and previous studies were confined to a single factor which acts on a single tissue. An ovariectomized dog model that is established in this study is used for simulating the change of lumbar vertebra and adipose tissue after menopause.The lumbar vertebra and adipose tissue be considered as a whole subject in this study, and we explore the change of distribution, ingredients, quantity, structure, blood perfusion,and secretion of the two tissues in the ovariectomized dog model. We study the relationship and mechanism of the lumbar vertebra and adipose tissue interactions by radiological technology， molecule and cell technology, and histopathological technology. The study also aims to find some techniques, which could evaluate the loss of bone and muscle, adipose tissue distribution easily, accurately and economically, to help early diagnosis of these musculoskeletal diseases. We also explore how to apply these techniques to perfect the treatment of the loss of bone after menopause.

绝经后女性骨骼丢失性疾病发病率高，严重影响生存质量，成为一个重大且不断增长的社会健康问题。绝经后体脂重新分布及数量变化与该疾病有着密切的关系。在性激素减少的背景下，骨骼、脂肪两种组织间应当存在一套整体的交互作用调控机制，但目前该调控机制仍未明确，且既往的研究多局限于单一因素对单一组织的影响。本项目拟通过建立模拟绝经后腰椎骨、腹部脂肪变化的雌性去势比格犬实验模型，把腰椎骨、腹部脂肪作为整体，从全局上探讨在绝经后犬动物模型中，两者在分布、成分、数量、结构、血流灌注、分泌等方面发生的变化，通过影像学、分子细胞学、组织病理学等技术手段从多个层面揭示绝经后腰椎骨、腹部脂肪两者交互作用关系及机制；并寻找易行、准确、经济的临床评价骨骼丢失性疾病、体脂重新分布的技术方法，为早期、准确诊断绝经后骨骼丢失性疾病提供帮助，并探讨如何应用这些方法来改善治疗手段。

背景：绝经后随着体内激素水平的变化,脂肪代谢和分布发生变化，呈向心性肥胖,腹部脂肪特别是内脏脂肪增多。研究证实绝经引起雌激素减少是导致腹内脂肪组织增多的主要因素，可能与雌激素调节脂肪细胞因子、作用于雌激素受体及调节脂肪细胞增殖分化有关。本研究通过卵巢切除术后比格犬模型，研究绝经后血清学指标、腹部脂肪量、腰椎骨密度、椎体骨髓脂肪含量的变化趋势及其相互关系。研究内容：选取8只成年雌性比格犬，随机选6只行卵巢切除术，2只行假手术，分别在术前和术后不同时间段行测量血清学指标、QCT腰椎骨密度、腹部脂肪面积和肝脏脂肪含量、MRI腰椎骨髓脂肪。分别比较实验组术后不同时间影像学结果和血清学结果与术前结果的差异，并比较实验组和对照组同一时间的影像学结果和血清学结果。实验组血清学指标与影像学指标分别做相关性检验。结果及关键数据：实验组术后6个月和10个月腰椎骨密度值较术前明显升高（p = 0.28），腰椎骨密度与血清雌激素(r = -0.427, p = 0.037）、内脂素（r = -0.508，p = 0.022）水平呈负相关。实验组术后6个月（p = 0.028）、10个月（p = 0.046）腹内脂肪面积较术前升高明显，腹内脂肪面积与雌激素 r = -0.462，p = 0.023），瘦素（r = -0.424，p = 0.039）呈负相关。术后各期骨髓脂肪含量与术前相比均无显著变化。科学意义：卵巢切除术后比格犬动物模型可用于研究绝经后雌激素缺乏所引起的脂肪代谢变化，分析相关脂肪因子与体内脂肪再分布的关系。卵巢切除术后比格犬逐渐出现腹部脂肪堆积，术后6个月以后腹腔内脏脂肪显著增加，腹腔内脏脂肪含量与雌激素和瘦素水平有关。绝经后比格犬骨髓脂肪含量与腹部脂肪含量变化趋势不一致。对比格犬切除双侧卵巢观察10个月无法建立绝经后骨质疏松模型。