Molecular hydrogen regulates PTEN-AKT-mTOR signaling via ROS to alleviate peritoneal dialysis-related peritoneal fibrosis
Molecular hydrogen regulates PTEN-AKT-mTOR signaling via ROS to alleviate peritoneal dialysis-related peritoneal fibrosis
复制标题
氢分子通过ROS调节PTEN-AKT-mTOR信号传导以减轻腹膜透析相关的腹膜纤维化
DOI：
10.1096/fj.201901981r
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发表时间：
2020-01-12
期刊：
影响因子：
4.8
通讯作者：
Guo, Zhiyong
中科院分区：
文献类型：
--
作者：
Lu, Hongtao;Chen, Wei;Guo, Zhiyong
腹膜透析是治疗终末期肾病（ESRD）的一种方便、有效、经济的肾脏替代疗法，全球约有11%的ESRD患者接受腹膜透析。然而，长期腹膜透析治疗会导致腹膜纤维化。近年来，分子氢在生物医学领域的应用潜力得到了广泛的认可。分子氢选择性清除细胞毒性活性氧（ROS），并作为抗氧化剂。本实验通过腹腔注射高糖腹膜透析液成功建立了高糖诱导的腹膜纤维化小鼠模型，并采用富氢腹膜透析液对腹膜纤维化小鼠进行治疗。此外，使用MeT-5A细胞进行了高葡萄糖诱导的腹膜纤维化的体外研究。体内外实验表明，分子氢能有效抑制高糖诱导的腹膜纤维化进程。此外，已经发现分子氢通过消除细胞内ROS和抑制PTEN/AKT/mTOR途径的活化来减轻纤维化。目前的数据表明，分子氢通过ROS/PTEN/AKT/mTOR通路发挥抗腹膜纤维化的能力。因此，分子氢是一种潜在、安全、有效的治疗药物，具有腹膜保护作用，具有重要的临床意义。
As a convenient, effective and economical kidney replacement therapy for end-stage renal disease (ESRD), peritoneal dialysis is available in approximately 11% of ESRD patients worldwide. However, long-term peritoneal dialysis treatment causes peritoneal fibrosis. In recent years, the application potential of molecular hydrogen in the biomedicine has been well recognized. Molecular hydrogen selectively scavenges cytotoxic reactive oxygen species (ROS) and acts as an antioxidant. In this experiment, a high glucose-induced peritoneal fibrosis mouse model was successfully established by intraperitoneal injection of high glucose peritoneal dialysate, and peritoneal fibrosis mice were treated with hydrogen-rich peritoneal dialysate. In addition, in vitro studies of high glucose-induced peritoneal fibrosis were performed using MeT-5A cells. In vitro and in vivo experiments show that molecular hydrogen could inhibit peritoneal fibrosis progress induced by high glucose effectively. Furthermore, it has been found that molecular hydrogen alleviate fibrosis by eliminating intracellular ROS and inhibiting the activation of the PTEN/AKT/mTOR pathway. The present data proposes that molecular hydrogen exerts the capacity of anti-peritoneal fibrosis through the ROS/PTEN/AKT/mTOR pathway. Therefore, molecule hydrogen is a potential, safe, and effective treatment agent, with peritoneal protective property and great clinical significance.