硫氧还蛋白系统及在砷致肝损伤中的作用机制研究进展

The role and mechanisms of thioredoxins in arsenic-induced liver injury

硫氧还蛋白（thioredoxin，TRX）是硫氧还蛋白系统中最重要的物质，后者还包括硫氧还蛋白还原酶（thioredoxin reductase，TRXR）和还原型辅酶Ⅱ（NADPH）。广泛表达的TRX作为蛋白质二硫键的还原酶，参与很多生理过程，并发挥重要生物学功能，包括调节机体的氧化还原反应、抑制细胞凋亡、调节转录因子DNA结合活性以及免疫应答等，其中一个重要作用是参与调节细胞氧化还原状态以对抗氧化应激。流行病学调查显示，高砷暴露人群血中活性氧水平显著升高，抗氧化物质水平显著下降。砷通过诱导氧化应激对肝细胞产生损害，脂质过氧化进程中的氧化应激机制一直是被广为认可和深入研究的砷中毒主要机制之一，此进程中可以产生多种自由基和非自由基产物，可引起肝细胞功能紊乱或直接攻击肝细胞造成损伤。作者主要对TRX系统在砷致肝损伤中的抗氧化应激作用进行综述。

Thioredoxin （TRX） is an important component in the thioredoxin system which is comprised of TRX, thioredoxin reductase （TRXR）, and reduced coenzyme Ⅱ （NADPH）. TRX is widely expressed in nearly all living cells and functions as protein disulfide reductase involving in many important biological processes, including redox signaling, the inhibition of apoptosis, regulation of transcription factors, and immune responses. TRX plays an important role in the regulation of the intracellular redox state against oxidative stress. Epidemiological studies showed that high arsenic exposure led to significant increases of serum levels of reactive oxygen species and decreases of antioxidant levels. Liver cell injury induced by arsenic via oxidative stress has been extensively studied. Oxidative stress in the process of lipid peroxidation has been widely recognized as one of the main mechanisms of arsenic poisoning. This process can produce a variety of free radicals and non-radical products those cause liver cell dysfunction or directly attack liver cells causing liver damage. Therefore, we hypothesized that TRX could play an important protective role in arsenic-induced liver injury. This paper reviews the antioxidative role of TRX in the liver injury caused by arsenic poisoning.