主动脉夹层（AD）呈血管壁退行性改变及扩张，破裂后死亡率达90%。炎症小体过度激活促进AD发生，但内源性保护机制研究尚少。我们前期发现ST2是AD特异标志物，ST2敲除显著增加AD发生及破裂率，而IL33/ST2活化可抑制AD形成及NLRP3炎症小体激活，提示IL33/ST2对AD具有保护作用；进而发现ST2敲除引发平滑肌细胞凋亡，而IL33/ST2活化可激活MAPKp38/JNK/ERK通路，上调抗凋亡基因，减轻凋亡，我们提出假设：IL33/ST2失活可能激活NLRP3炎症小体及下调MAPK通路调节凋亡而引起AD。本研究拟在野生、ST2敲除及条件敲除小鼠中诱导AD，结合病理、分子生物学、蛋白质组学等分析，明确高血压如何诱导IL33/ST2活性改变，IL33/ST2如何抑制炎症小体活化、上调MAPK通路，从而抑制平滑肌细胞表型转化、凋亡，维持细胞外基质稳定，保护AD发生的具体机制。

Aortic dissection (AD) showed features of degeneration and dialation, with its mortality up to 90% once ruptured. Several signaling pathways, like the NLRP3 inflammasome pathway plays a critical role in AD formation, while the endogenous protective molecular mechanism remains unclear. Our previous study showed that sST2 was an independent biomarker for early diagnosis of AD. ST2 deficiency aggravated AD formation and aneurysm rupture, and IL33 treatment decreased the maximal diameter and severity of AD and inhibited NLRP3 expression, which suggested the protective role of IL33/ST2 in AD formation. Moreover, there were accumulated smooth muscle cells apoptosis in angiotensin II infused-ST2 knockout mouse aorta, which could be blocked by IL33 treatment. Furthermore, the expression of IL33 was upregulated in vascular fibroblasts in case of mechanical overload. Therefore, we hypothesized that IL33/ST2 deficiency upregulated NLRP3 inflammasome activity after angiotensin II infusion, and downregulated MAPKp38/JNK/ERK pathway to promote smooth muscle cell apoptosis, leading to AD. In the present study, we will induce AD formation in wild type and ST2 knockout mice, as well as ST2 conditional knockout mice to clarify the protective role of IL33/ST2 in Ang II infusion-induced AD formation by performing bone marrow transplantation, echography, pathological analysis and quantitative and modification proteome analysis in vitro.