硝酸盐转运通道与游离组织瓣缺血再灌注损伤的相关性研究

Nitrate-Nitrite-NO pathway delivers significant physiological functions. Nitrate, NO, and Nitrate-NO pathway develop an important pathophysiological role in the process of ischemia reperfusion ( I/R ). The function of Nitrate -NO pathway and Nitrate transport channel between cells and tissues have not been reported in the process of I/R after free flap transplantation. Our previous study found that Sialin,which is translated by SLA17A5,functions as a Nitrate transport channe in salivary glands. Up to now, the expression and distrabution of SLA17A5 in the free flaps is still undiscovered. And the correlation between SLA17A5 and Nitrate in the process of ischemia reperfusion has not been reported. This study is conducted to reveal the expression and localization of SLC17A5 in the free flaps via establishment of animal models, immunohistochemistry, immunofluorescence, Western blot and RT-PCR. The interrelationship and feedback mechanism between Nitrate transport channel, Nitrate, NO, and nitric oxide synthetase in the process of I/R will be explored through SLC17A5 expression and NO probe analysis. Finally, for the prognostic evaluation, the correlation between Nitrate -NO pathway and the success rate of the transplantation will be probed by using animal models and clinical cases analysis. This exploration may provide new ideas and methods for improving the success rate of free flap transplantion.

硝酸盐-亚硝酸盐-NO途径具有非常重要的生理功能。硝酸盐、亚硝酸盐以及NO在组织缺血再灌注（I/R）过程中发挥重要的病理生理作用。而在游离组织瓣I/R过程中硝酸盐-NO途径以及硝酸盐在细胞与组织间的转运通道未见报道。本课题组成员前期研究发现SLA17A5编码的Sialin蛋白是唾液腺腺硝酸盐转运通道，而其在游离组织瓣组织中的表达和分布还不清楚。其在I/R过程中与NO及硝酸盐的相关性研究还未见报道。本研究旨在通过建立动物模型、免疫组化、免疫荧光、western blot及RT-PCR等方法研究SLC17A5在游离组织瓣中的表达，组织定位。通过SLC15A5基因表达、NO探针等方法研究在I/R过程中硝酸盐转运通道与硝酸盐、NO、一氧化氮合成酶的相互关系，以及反馈机制。通过人游离组织瓣移植病例及建立动物模型研究游离组织瓣移植缺血及再灌注过程不同时点中硝酸盐-NO途径与移植预后的关系。为改善游离组织瓣移植预后提供新的思路和方法。

《硝酸盐转运通道与游离组织瓣缺血再灌注损伤的相关性研究》主要通过构建动物模型、蛋白质及mRNA分析技术、生化检测技术等研究硝酸盐转运通道（SLC17A5）与游离组织瓣缺血再灌注损伤的相关性。通过研究发现，硝酸盐转运通道在血管组织内高表达，并且建立大鼠游离组织瓣缺血再灌注损伤实验的动物模型，利用动物模型研究发现硝酸盐转运通道与组织瓣缺血再灌注损伤密切相关。在本课题资助下，发表国内核心期刊论文一篇，投稿SCI杂志论文两篇，培养硕士研究生两名。