动脉粥样硬化（AS）是一种多因素导致的慢性炎症疾病。IL-6/gp130信号通路的激活对AS的发生发展具有促进作用。因此，抑制该信号通路的活化是AS防治研究的热点。近年来，神经-内分泌-炎症网络学说为冠心病的病理生理过程做出了新的解释，根据此学说，申请者前期研究表明，绝经后女性冠心病患者体内雌/雄激素比例会发生失衡，血清hsCRP水平也与雌雄激素比例呈显著负相关，提示雌雄激素比例失衡会引起炎性因子表达上调是促使AS进行性发展的重要因素。进一步细胞学研究发现，在HUVECs中给予雌雄激素联合给药可明显下调gp130蛋白的水平，提示雌雄激素协同作用可通过抑制gp130的水平发挥抗炎效应。本研究拟在现有研究基础上深入探讨雌雄激素协同作用对IL-6/gp130信号通路的抑制及其抗动脉粥样硬化的分子机制，为冠心病的防治提供新思路；通过gp130的检测，提示gp130可以作为启动AS进程的新靶标。

Atherosclerosis (AS) is a chronic inflammatory response disorder. IL-6/gp130 signaling pathway stimulates the development of 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. Recently, the theory of the nerve-endocrine-inflammation network provides a new explanation for the pathophysiologic process of coronary heart disease (CHD). According to this theory, the applicant’s previous research showed that the balance of the serum estradiol and testosterone ratio was broken in postmenopausal women with CHD, and an imbalanced estradiol and testosterone ratio showed a strong association with hsCRP. This indicates that the imbalanced estradiol and testosterone ratio can upregulate the inflammatory factors which may be a crucial cause of the development of AS. Furthermore, in HUVECs, estradiol combined with testosterone can significantly downregulate the expression of gp130, which indicates that the synergistic effect of estradiol and testosterone can reduce the inflammation through the reduction of the level of gp130. This research will be based on the applicant’s present results, and will be followed by discussion of the inhibition of the synergistic effect of estradiol and testosterone in the IL-6/gp130 signaling pathway. Finally, the focus will be on determining the molecular mechanism of the anti-atherosclerotic effect, which would provide new ideas and a target for AS treatment.