硝酸盐转运蛋白Sialin在组织瓣缺血再灌注损伤中的作用机制研究

Ischemia-reperfusion injury (IRI) is one of the important factors affecting the survival rate of flaps transplantation. The generation of the nitric oxide protects the tissue from the process of ischemia reperfusion. As a major transporter of the nitrate for mammals, Sialin plays an important role in maintaining nitrate and nitric oxide balance in the body. Previous studies have found that Sialin, which is high expressed in vascular endothelial cell (VEC), is closely related to IRI of free flaps. This project intends to confirm that the Sialin exercise the transport function in VEC. By the way of regulating the expressing level of Sialin and construct a cell IRI model with VEC, we are going to clarify the influence of nitrate, which as the precursor of the NOS-independent NO generation, on IRI of the VEC and investigate the mechanism of Sialin that protected the tissue from IRI. This program will reveal the fact that Sialin can reduce IRI of VEC by transporting enough nitrate which as the precursor of the NOS-independent NO generation into VEC. And this research is expected to provide new ideas and methods to improve IRI's therapy.

缺血再灌注损伤是影响游离组织瓣成活的重要因素之一。一氧化氮的生成在缺血再灌注过程中起到保护作用。Sialin是哺乳动物硝酸盐转运蛋白，对维持硝酸盐——一氧化氮平衡有重要作用。本课题组前期研究证实了Sialin在血管内皮细胞中高表达，并且与组织瓣缺血再灌注损伤密切相关。本课题拟证实Sialin在血管内皮细胞中具有硝酸盐转运功能；构建细胞缺氧/复氧模型，并通过基因工程调控血管内皮细胞内Sialin表达水平，阐明非酶源途径一氧化氮前体硝酸盐对血管内皮细胞缺血再灌注损伤的影响，探讨Sialin在缺血再灌注损伤中起保护作用的机制。本项目有望揭示Sialin通过转运硝酸盐，为非酶源途径一氧化氮的产生提供足够的前体，从而减轻血管内皮细胞在缺血再灌注过程中的损伤。为组织瓣缺血再灌注损伤的治疗提供新思路和方法。

Sialin是哺乳动物硝酸盐转运蛋白，对维持全身硝酸盐及一氧化氮平衡有重要作用。缺血再灌注损伤是影响组织瓣移植后成活的重要因素之一。本课题通过建立动物和细胞缺血再灌注损伤模型，发现Sialin与缺血再灌注损伤密切相关，而硝酸盐在其中更是起到了关键性的作用。同时本项目资助研究发现硝酸盐不仅仅是在缺血再灌注损伤中起作用，在炎症状态下也起作用，进一步验证了硝酸盐治疗的广泛性与重要性。本项目资助共已发表核心期刊5篇，SCI 7篇，仍有一篇核心期刊，一篇SCI论文等待发表（已经标注基金号）。培养硕士研究生三名，资助博士研究生一名完成博士课题（毕业论文撰写中）。