IL-35和IL-12在IL-12p35-/-小鼠腹主动脉瘤模型中的作用和机制研究

与动脉粥样硬化一样，腹主动脉瘤（AAA）是一种巨噬细胞和T淋巴细胞介导的致命性的慢性炎症性疾病。新型抗炎因子IL-35与促炎因子IL-12同属IL-12家族，两者有共同的p35亚基，均通过调控巨噬细胞和T淋巴细胞活性参与慢性炎症性疾病进程。本课题组的前期研究提示，IL-35和IL-12与动脉粥样硬化性疾病的发生发展密切相关；预实验成功构建一种新型AAA模型：血管紧张素II（Ang II）灌注IL-12p35敲除(p35-/-)小鼠AAA模型。但是，p35-/-小鼠AAA的发生与IL-35或IL-12有何种关系及相关机制仍不清楚。本研究采用Ang II诱导p35-/-小鼠AAA模型，分别给予不同剂量IL-35和IL-12，并在信号通路关键分子进行干预，以阐明IL-35、IL-12调控AAA发生发展的机制，为AAA防治的新思路提供实验依据。

Abdominal aortic aneurysm (AAA), like atherosclerosis, is a fatal chronic inflammatory disease characterized by macrophages and T lymphocytes infiltration. However, there is no effective medical therapy for the prevention or treatment of AAA. The anti-inflammatory cytokine interleukin (IL) 35 and the pro-inflammatory cytokine IL-12 belong to the IL-12 family and have the same subunit p35. Evidence showed that p35 knockout abolishes the biological activity of IL-35 and IL-12. Both IL-35 and IL-12 take part in chronic inflammatory disease by regulating the activity of macrophage and T lymphocyte. Our previous studies indicated that IL-35 and IL-12 are involved in atherosclerosis. The pre-experiment found that treatment with angiotensin II infusion resulted in AAA in p35-/- mice. However, the role of IL-35 and IL-12 in AAA formation remains uncertain. In vivo and vitro experiments are going to be performed around the effect and mechanism of IL-35 and IL-12 on inflammatory regulation and AAA formation in p35-/- mice. This study will provide experimental evidence for comprehensive evaluation about IL-35 and IL-12 as targets for the treatment of AAA.