胰岛素抵抗（IR）状态下动脉粥样硬化（IR-AS）斑块进展快，稳定性差，死亡率高，探索IR-AS有效干预策略是亟需解决的关键科学问题。脂肪因子分泌失衡是IR导致AS快速进展的可能促进因素。我们前期研究发现，抗炎性脂肪因子CTRP9血清水平与冠脉斑块稳定性呈正相关，CTRP9可通过调控血管平滑肌细胞（VSMCs）表型转换抑制AS进展，但CTRP9是否与IR-AS密切相关尚不清楚。因此，本研究拟构建IR-AS相关动物模型，明确脂肪因子CTRP9的水平与IR-AS斑块稳定性的关系，验证科学假设：IR状态下CTRP9通过AMPK/TET2/5hmc通路调节VSMCs表型转换抑制IR-AS进展；探索在体主动调控CTRP9水平对IR-AS进展的影响。本项目研究结果将为IR-AS防控提供新的思路和干预策略，特别是如果证明外源性CTRP9可抑制IR-AS进程，将为临床IR-AS的防控提供可行的治疗策略。

Atherosclerosis (IR-AS) plaque under insulin resistance (IR) condition progresses rapidly, has poor stability and high mortality. Exploring effective intervention strategies for IR-AS is a key scientific problem to be solved urgently. The imbalance of adipokine secretion is a possible contributor to the rapid progress of AS induced by IR. Our previous studies have found that serum levels of anti-inflammatory adipokine CTRP9 are positively correlated with the stability of coronary plaque. CTRP9 can inhibit the progression of AS by regulating the phenotype transition of vascular smooth muscle cells (VSMCs), but whether CTRP9 is closely related to IR-AS is unclear. Therefore, this study intends to construct an IR-AS related animal model to clarify the relationship between the level of adipokine CTRP9 and the stability of IR-AS plaque, and to verify the scientific hypothesis that CTRP9 inhibits the progress of IR-AS by regulating the phenotype transition of VSMCs through AMPK/TET2/5hmc pathway under the state of IR, and to explore the effect of active regulation of CTRP9 level on the progress of IR-AS in vivo. The results of this project will provide new ideas and intervention strategies for the prevention and control of IR-AS. Especially, if exogenous CTRP9 can inhibit the process of IR-AS, it will provide a feasible treatment strategy for the prevention and control of clinical IR-AS.