衣康酸通过下调IκBζ调控Th17/Treg平衡并减轻肝移植缺血再灌注损伤的功能机理研究

供肝缺血再灌注损伤（IRI）严重制约了肝移植的疗效和供体来源。治疗肝移植IRI的关键在于控制炎性免疫失衡。衣康酸是炎症状态下大量产生的细胞代谢物，已知能促进炎症消退，但其对肝移植IRI的作用尚不清楚。我们前期研究发现衣康酸在肝移植后大量产生，并能减轻肝移植IRI。转录调控蛋白IκBζ在多种免疫细胞表达，它能促进Th17分化并抑制Treg分化，并能促进Th17分泌IL-17，从而促进炎症。我们前期发现衣康酸可下调初始CD4+T细胞IκBζ表达，并能降低肝移植后IL-17水平，提高IL-10水平。据此，我们推测衣康酸可通过下调IκBζ促进Th17/Treg平衡向Treg方向转化，从而促进炎症消退，减轻肝移植IRI。本课题拟明确肝移植中衣康酸的代谢通路变化，分析衣康酸促进肝移植IRI中炎症消退的功能机理，为肝移植IRI的防治提供新思路。

Ischemia reperfusion injury (IRI) of donor liver severely restricts the therapeutic effect and donor source of liver transplantation. The key to prevent IRI is to control the imbalance of inflammatory immune response. Itaconate is a metabolite induced by macrophages in inflammation. It is known that itaconate can promote inflammatory regression, but its function in liver transplantation is not clear. Our previous study found that itaconate were produced a lot after liver transplantation and alleviated IRI. The transcription regulatory protein IκBζ is expressed in a variety of immune cells. Its function includes promoting Th17 differentiation, inhibiting Treg differentiation, and promoting IL-17 production. We found that itaconate decreased the level of IκBζ protein, decreased the level of IL-17 and increased the level of IL-10 after liver transplantation. Therefore, we speculated that itaconate could shift Th17/Treg balance to Treg predominance by downregulating IκBζ, so as to promote inflammation regression and alleviate IRI in liver transplantation. The purpose of this study is to clarify the metabolic change of itaconic acid in liver transplantation, analyze the functional mechanism of itaconate in promoting inflammatory regression in liver transplantation IRI, and explore a new therapeutic target to effectively prevent liver transplantation IRI.