基于营卫理论探索桂枝汤上调Rev-erbα节律因子抑制CCL5介导的PVAT炎症治疗动脉粥样硬化的研究

血管周围脂肪（PVAT）炎症浸润可加速动脉粥样硬化（AS）斑块形成，趋化因子可介导促炎细胞浸润，并接受外周生物钟系统的调节。流行病学也显示不规律作息导致AS与生物钟紊乱有关。本项目结合中医营卫经典理论，力求阐明生物钟基因Rev-erbα靶向抑制趋化因子CCL5的表达而减轻PVAT中促炎细胞浸润，从PVAT生物钟失衡角度探索防治AS的新机制。课题组前期已证明调和营卫经方桂枝汤可抑制心脏血管炎症反应，调节心血管交感/迷走神经支配失衡。在此基础上，本项目拟ApoE-/-小鼠、单纯生物钟系统紊乱小鼠、脾细胞为模型，桂枝汤灌胃同步给予Rev-erbα抑制剂，体内体外实验结合，阐释“桂枝汤靶向Rev-erbα恢复生物钟平衡，抑制PVAT中促炎细胞浸润，减轻动脉粥样硬化”的科学假说。为防治AS提供新方法和科学依据。并进一步从调控生物钟平衡，揭示营卫理论的现代科学内涵。

Inflammation around perivascular adipose tissue promotes the development of atherosclerosis (AS). Chemokine mediates pro-inflammatory cell infiltration, and accepts the modulation derived from biological clock molecular. Epidemiology studies show that irregular work schedule leads to circadian clock disorder, which promotes the development of AS. In the present study, under guidance of Traditional Chinese Medicine theory of Ying-Wei, we try to demonstrate that activating Rev-erbα could prevent AS by inhibiting CCL5 mediate pro-inflammatory cell infiltration, and explore a new treatment pathway of AS through recovering biological clock balance in PVAT. Our previous studies have been demonstrated that Guizhi decoction inhibit cardiovascular inflammation and improve vagus-sympathetic imbalance. Based on these results, by use of ApoE-/- mice, mice with disordered biological clock, spleen cell model, Rev-erbα antagonist, we will further demonstrate that Guizhi decoction could suppress CCL5-mediated inflammation in PVAT by up-regulating the expressions of Rev-erbα and recovering biological clock balance in vitro and in vivo. Our study not only provide new methods and scientific basis for treatment of AS, but also illustrate the scientific connotation of Ying-Wei theory in term of biological clock system, autonomic nerve system and immunity system.