PSTK基因/GPx-1/过氧化氢信号通路异常是百草枯所致肺损伤的重要机制

百草枯(PQ)中毒死亡率高，其直接死因为急性肺损伤(ALI)。前期我们检测了PQ中毒肺组织基因表达谱，确定了35个关键调控基因，其中PSTK是唯一调控硒蛋白的基因；PSTK基因和蛋白表达与PQ中毒小鼠肺损伤程度成负相关；PQ中毒PSTK基因敲除线虫和PSTK基因敲除小鼠生存时间均显著缩短；百草枯中毒患者血液PSTK水平较正常人显著降低 。由于硒蛋白GPx-1主要通过还原过氧化氢（H2O2）为水而起抗氧化作用，且PQ中毒的GPx-1基因敲除小鼠生存时间显著缩短而过表达则显著延长；PSTK通过调控硒代半胱氨酸而调控GPx-1功能，故认为PSTK/GPx-1/H2O2信号通路异常是PQ致肺损伤的重要机制。为此，拟采用基因工程小鼠通过阐明肺PSTK基因的生理作用和PSTK/GPx-1/H2O2通路在PQ所致肺损伤中的作用机理，为研究基于干预PSTK基因和采用硒蛋白联合治疗PQ中毒新方案提供证据。

Paraquat (PQ) poisoning caused high mortality in China . Its main cause of death is oxidative stress-induced lung injury. Previously, we assayed gene spectrum of lung tissue of PQ-induced lung injury, and identified 35 core genes related to PQ poisoning. Among them, phosphoseryl-tRNA kinase (PSTK) is the only gene that is related to selenium proteins, and we also observed that knockout of PSTK gene in both C-elegans and mice model exhibited shorter survival time than wide type when challenged by PQ. The blood PSTK level in healthy volunteers was much lower than that in patients with PQ poisoning. In addition, Glutathione peroxidase-1 (GPx-1) is an intracellular antioxidant enzyme that enzymatically reduces hydrogen peroxide to water to limit its harmful effects. Knockout of GPX-1 in both Caenorhabditis elegans and in C57BL/6 mice shortens their survival time. PSTK influences the function of selenoproteins through the selenocysteine insertion sequence. Thus, we hypothesized that the aberrant PSTK/GPx-1/H2O2 signaling plays a key role in PQ-induced acute lung injury (ALI). To confirm this, we initially investigate the physiological role of PSTK, and function of PSTK/GPx-1/H2O2 signaling in pathological mechanism of PQ induced ALI. Our studies will not only deepen the understanding of mechanism of PQ-induced ALI, but also provide a promising treatment of using both PSTK intervention and selenoprotein.