糖尿病性骨质疏松（DOP）是糖尿病在骨骼系统中的严重并发症，但骨质疏松的治疗对糖尿病患者骨骼的影响并不明确。我们在前期研究中发现大豆异黄酮（SI）的代谢产物雌马酚（Eq）能够显著改善去卵巢大鼠骨质疏松，促进成骨细胞（OB）增殖分化，并且该作用与雌激素受体β（ERβ）密切相关。但是Eq的骨保护作用在糖尿病患者中的作用及其机制还不清楚。我们推测Eq在高糖条件下主要通过雌激素受体β调控IGF-1等基因表达，并协同雌激素膜受体，激活MAPK/ERK、PI3K/AKt等信号通路来促进OB增殖。为此本研究拟通过建立DOP大鼠模型和ER沉默OB模型，检测Eq对OB中ER介导的转录激活作用及相关信号通路基因表达变化，并初步探索这个过程中雌激素核受体和膜受体的协同作用，阐明Eq在高糖条件下通过ER途径调控OB增殖防治DOP的分子机制。研究结果将为进一步探索DOP发病机制及其防治效应提供新的理论和实验依据。

Diabetic osteoporosis (DOP) is a severe complication of diabetes mellitus in the skeletal system, but the effect of the treatment methods of osteoporosis to the bone of patients with diabetes is not clear. we found in the previous study that the metabolite Equol (Eq) of soybean isoflavones (SI) can significantly improve osteoporosis in ovariectomized rats, promote the proliferation and differentiation of osteoblast (OB) , and the effects are closely related to the estrogen receptor beta (ERβ). However，the effect of bone protection with Eq in patients with diabetes and its mechanism is unknown. We hypothesized that under the condition of high sugar，Eq mainly regulates the expression of the IGF-1 and other genes through the estrogen receptor beta, cooperating with the membrane estrogen receptors, to activate the MAPK/ERK and/or PI3K/AKt signaling pathways to promote osteoblast proliferation. Therefore，in this study we plan to establish the rat model with DOP and OB model with ER gene silencing, detect of ER mediated transcription activation effect and gene expression changes in related signaling pathways, and preliminarily explore the synergistic effect of nuclear receptor and membrane estrogen receptor, to clarify the effect and mechanism of S-Equol on osteoblast proliferation under the condition of high glucose through ER pathway to prevent and treat diabetic osteoporosis. The results will provide new theoretical and experimental basis for further exploring the pathogenesis and prevention and treatment effects of DOP.