氧化应激是缺血再灌注诱发的急性肾损伤（AKI）发病机制中的重要环节，在CRRT患者中高氧化应激状态尤为显著。这些活性氧自由基（ROS）可诱导肾小管上皮细胞凋亡、加重肾功能损伤。氢气可减少ROS产生，在急性脑缺血性卒中、急性心肌梗塞、急性肝损伤等研究中陆续被发现可抑制细胞凋亡、减轻氧化应激损伤，因而理论上亦可以改善急性肾脏缺血再灌注损伤诱导的细胞凋亡，但其抗凋亡机制尚未阐明。近期研究发现LKB1（STK11）可通过将p53的Ser15磷酸化，激活LKB1-p53-p21/WAF1途径、促进细胞凋亡。因此，本研究拟首先构建急性大鼠肾脏缺血/再灌注模型并采用富氢置换液行CRRT治疗，观察富氢置换液能否改善大鼠肾脏缺血/再灌注损伤，同时通过体内、体外实验共同探讨ROS-LKB1-p53-p21/WAF1途径在氢气治疗减少细胞凋亡、减轻急性肾脏缺血/再灌注损伤中的作用。

Oxidative stress plays an important role in the pathogenesis of acute kidney injury (AKI) induced by ischemia-reperfusion.Reactive oxygen species(ROS), especially in patients treated with continuous renal replacement therapy(CRRT), induces severe apoptosis of renal tubular epithelial cell and predicts poor prognosis. It is proved that hydrogen (H2) can inhibit apoptosis in acute ischemic stroke, myocardial infarction, acute liver injury, etc. The mechanisms of the inhibiting effect of apoptosis remain unknown. LKB1 as a kind of serine/threonine kinase can induce apoptosis via LKB1-p53-p21/WAF1 pathway by phosphorylating p53 at Ser15. Our study purposes to clarify whether hydrogen-rich hemofiltration solution improves renal ischemia-reperfusion injury with CRRT in rats. We will further explore the effect of ROS-LKB1-p53-p21/WAF1 pathway in apoptosis of renal tubular epithelial cell induced by renal ischemia-reperfusion injury.