IL-6/gp130信号通路的激活是促进动脉粥样硬化（AS）发生发展的关键因素。如何抑制该信号通路的活化及相关分子机制研究是目前AS防治研究的热点。申请者前期基金研究发现，雌雄激素协同作用可明显抑制gp130蛋白的表达，雌激素受体α和β均可与gp130结合从而改变gp130的蛋白质结构与功能，抑制下游信号通路的激活，起到抗AS的作用。然而，雌激素/雌激素受体对gp130蛋白水平、结构与功能影响的具体机制尚不明确。本研究拟在前期基金研究基础上，进一步在细胞水平探讨雌激素/雌激素受体对gp130蛋白表达抑制效应以及雌激素受体与gp130结合的分子机制，利用ApoE-/-伴gp130CD-/-鼠验证雌激素/雌激素受体影响gp130水平、结构及功能的分子机制，为雌雄激素协同作用抑制IL-6/gp130信号通路从而发挥抗炎抗AS效应提供更详尽的理论基础，为gp130作为AS防治的新靶标提供实验依据。

IL-6/gp130 signaling pathway is the key factor in stimulating the development of Atherosclerosis (AS). Therefore, inhibition of the activity of IL-6/gp130 signaling pathway becomes a hot topic in the field of prevention and treatment of AS. The applicant’s previous research showed that estradiol combining with testosterone can significantly downregulate the expression of gp130. Both estrogen receptor α and β can bind with gp130 to interfere its function, inhibit the following signal transduction, finally have the anti-atherosclerosis effect. However, the mechanism of how does estrogen/estrogen receptor influence the expression, structure and function of gp130 is still unclear. This research will be based on the applicant’s present results, and will have a further study on the molecular mechanism on how does estrogen/estrogen receptor inhibit gp130 expression and how does estrogen receptor bind with gp130 using HUVECs and ApoE-/-gp130CD-/- mice, which would provide a more specific evidence in the anti-atherosclerosis effect of estradiol combining with testosterone by inhibiting the IL-6/gp130 signaling pathway, and for gp130, provide a research basic in becoming a new bio-marker in AS treatment.