基于AngⅡ/PPARγ/NF-κB炎症通路探讨益气活血方延缓血管的炎性衰老分子机制

炎性衰老是机体衰老的重要标志，其引起的血管的炎性衰老改变贯穿高血压发病的始终。血管紧张素Ⅱ（AngⅡ）、过氧化物酶体增殖物激活受体γ（PPARγ）及核因子κB（NF-κB）与衰老及炎症密切相关，但尚缺乏AngⅡ/PPARγ/NF-κB通路与血管的炎性衰老研究。前期发现，益气活血方延缓AngⅡ诱导的内皮衰老，通过PPARγ降低自发性高血压大鼠（SHR）平滑肌增殖，达到延缓血管细胞衰老作用，但可否通过AngⅡ/PPARγ/NF-κB通路延缓血管的炎性衰老尚不明确。本研究建立SHR血管衰老模型与AngⅡ诱导细胞衰老模型，采用基因转染和RNA干扰实现细胞PPARγ过表达与基因沉默及NF-κB p65基因沉默状态，探讨AngⅡ/PPARγ/NF-κB通路与血管的炎性衰老关系，明确益气活血方是否通过AngⅡ/PPARγ/NF-κB通路延缓血管的炎性衰老机制，阐明益气活血方祛瘀生新、通脉活络的科学内涵。

Inflamm-aging is an important hallmark of organism aging, which causes vascular inflamm-aging throughout the pathogenesis of hypertension. Angiotension Ⅱ (Ang Ⅱ), peroxisome proliferator activated receptor γ (PPARγ) and nuclear factor kappa B (NF-κB) are closely related to aging and inflammation, but there is no study on the relationship between Ang Ⅱ/ PPAR γ/ NF-κB inflammatory pathway and vascular inflamm-aging. Previous studies have found that Yiqi Huoxue formula could delay the endothelial aging induced by AngⅡ and reduce the proliferation of the smooth muscle cells of the spontaneously hypertensive rats (SHR) through PPARγ, so as to delay the aging of vascular cells. However, it is not clear whether Yiqi Huoxue formula could delay the vascular inflamm-aging through the inflammatory pathway of Ang Ⅱ/ PPAR γ/ NF-κB. In this study, we established the vascular aging model of SHR and the model of cell senescence induced by Ang Ⅱ. The technologies of the gene transfection and RNA interference are used to achieve the overexpression and gene silencing of PPAR γ and NF-κBp65 gene silencing, in order to explore the relationship between Ang Ⅱ/ PPAR γ/ NF-κB inflammatory pathway and vascular inflamm-aging, find out whether Yiqi Huoxue formula could delay the vascular inflamm-aging through Ang Ⅱ/ PPAR γ/ NF-κB pathway, and clarify the scientific connotation of Yiqi Huoxue formula for removing blood stasis and promoting new circulation.