CD4+CD25+Foxp3+调节性T细胞在PM2.5所致动脉粥样硬化形成中的作用及定心方的干预研究

吸入PM2.5可促进动脉粥样硬化(AS)形成并上调内脂素表达，但机制尚未阐明。CD4+CD25+Foxp3+调节性T细胞(Tregs)参与了AS形成，但在PM2.5所致AS过程中内脂素表达上调是否与调控Tregs有关尚不清楚。前期研究中我们报道定心方可通过抗炎、下调内脂素表达等抗AS形成，因此我们推测定心方可能通过调控Tregs下调内脂素表达而发挥抗PM2.5所致AS功效。本研究拟用ApoE-/-小鼠结合PM2.5吸入的方式建立PM2.5所致AS动物模型，以PM2.5颗粒物悬浮液对EA.hy926型血管内皮细胞染毒建立细胞模型，应用外源性Tregs、中和抗体、MAPKs信号通路抑制剂及RNA干扰等技术，分别从整体及分子水平探讨Tregs在PM2.5所致AS过程中对内脂素的调控及定心方干预机制。项目研究有望为阐明PM2.5促进AS形成机制提供新的作用靶点，并为中医药临床防治AS提供新的思路。

Air pollution is a pervasive environmental health hazard. Early studies have shown that chronic exposure to PM2.5 could contribute to atherogenesis and up-regulating the expression of visfatin, but the mechanism remains unclear. CD4+CD25+Foxp3+ regulatory T cells (CD4+CD25+Foxp3+ Tregs) has participated in the development of atherosclerosis, but whether the increasing of visfatin expression is regulated by CD4+CD25+Foxp3+ Tregs in atherogenesis induced by PM2.5 inhalation has not been elucidated. Our research group have recently reported that DingXin Recipe (DXR), a Chinese compound prescription which was made follow the traditional Chinese therapeutic principles “tonifying Qi and activating blood, eliminating phlegm and removing blood stasis”, was effective in preventing atherogenesis by suppressing expressions of inflammatory cytokines, regulating blood lipid, down-regulating visfatin expression and regulating regulatory T cells . We speculated that DXR may prevent atherogenesis by down-regulating visfatin expression through regulating CD4+CD25+Foxp3+ Tregs in atherogenesis induced by PM2.5 inhalation. ApoE knockout mice were fed with a western diet and treated with PM2.5 to establish PM2.5-induced atherosclerosis models, PM2.5 fine particles suspensions were added into vascular smooth muscle cells (VSMC) of mice to establish damaged cell models, then observe the effect of CD4+CD25+Foxp3+ Tregs in regulating visfatin expression in PM2.5-induced atherosclerosis and the interventive effect of DXR. The objective of this study was to reveal the potential targets and to provide more scientific basis for Chinese compound prescription in the prevention and treatment of atherosclerosis.