流行病学及动物研究提示慢性根尖周炎(CAP)可能是动脉粥样硬化(AS)的风险因素。而肠道菌群失衡可引起AS。课题组发现CAP可致动脉壁炎性反应，并引起大鼠血清C反应蛋白(CRP)与白细胞介素-6(IL-6)等炎症因子水平升高及随后肠道菌群组成与丰度改变。血清CRP及IL-6升高可增加肠壁通透性。据此提出假说：CAP可致血清CRP及IL-6升高触发肠壁通透性增加，从而改变肠道菌群组成及丰度，引发菌群失衡，血液中细菌成分及代谢产物作用于血管壁，最终促进AS。并猜测TLR4/MyD88为肠壁通透性改变致肠道菌群失衡的主要通路。.本研究拟建立AS-CAP小鼠模型，在分子、细胞、组织水平探究CAP、全身炎症因子、肠道菌群变化及AS间的相互联系；并通过肠菌移植证实后二者的因果关系；并采用基因敲除小鼠验证TLR4/MyD88信号通路。从而系统研究CAP引起的肠道菌群失衡在AS发生发展中的作用机制。

Epidemiological surveys and animals studies have indicated that chronic apical periodontitis (CAP) may be a risk factor of atherosclerosis (AS)...Accumulating evidences have shown that imbalance of gut microbiota could lead to AS. In our previous studies, it was found that CAP could induce inflammatory pathosis in artery walls. It was also observed that CAP could cause elevation of serum inflammatory mediators such as C-reactive protein (CRP) and interleukin-6 (IL-6) with subsequent alteration of diversity and richness of gut microbiota. It has been confirmed that permeability of the intestinal wall could be increased by elevation of systemic CRP and IL-6. Therefore, we hypothesize that CAP could cause an elevation of serum CRP and IL-6, which in turn increases permeability of the intestinal wall, alters the composition and abundance of intestinal flora, giving rise to dysbiosis of gut microbiota. Interaction between bacterial components and/or matabolites with vessel walls ultimately leads to AS. In addition, we speculate TLR4/MyD88 to be the main pathway from increased intestinal wall permeability to gut microbiota dysbiosis. ..In this study, AS-CAP mouse model is established to explore the correlation among CAP, systemic inflammatory mediators, gut microbiota alteration, and AS at molecular, cellular and tissue levels. And, intestinal flora transplantation is conducted to verify the causal link between gut microbiota dysbiosis and AS. Furthermore, knock-out animals are used to testify the TLR4/MyD88 signal pathway. The objective of this study is to investigate the role and mechanism of CAP-induced gut microbiota dysbiosis in the development of AS.