PDF(Pubmed)
Abstract：
Postoperative acute kidney injury (AKI) is a common complication in patients undergoing deep hypothermic circulatory arrest (HCA); however, its underlying pathogenesis is unclear. In this study, we established a rat cardiopulmonary bypass model and demonstrated that hypothermia during HCA, rather than circulatory arrest, was responsible for the occurrence of AKI. By recruiting 56 patients who underwent surgery with HCA and analyzing the blood samples, we found that post-HCA AKI was associated with an increase in bradykinin. Animal experiments confirmed this and showed that hypothermia during HCA increased bradykinin levels by increasing kallikrein expression. Mechanistically, bradykinin inhibited the Nrf2-xCT pathway through B2R and caused renal oxidative stress damage. Application of Icatibant, a B2R inhibitor, reversed changes in the Nrf2-xCT pathway and oxidative stress damage. Finally, Icatibant reversed hypothermia-induced AKI in vivo. This finding reveals the pathogenesis of AKI after HCA and helps to provide therapeutic strategy for patients with post-HCA AKI.
摘要：
术后急性肾损伤(AKI)是深低温停循环(HCA)患者的常见并发症;其潜在的发病机制尚不清楚。在这项研究中,我们建立了大鼠体外循环模型，并证明了HCA期间的低体温，而不是拘禁，是AKI发生的原因。通过招募56名接受HCA手术的患者并分析血液样本，我们发现HCA后AKI与缓激肽增加相关.动物实验证实了这一点，并表明HCA期间的体温过低通过增加激肽释放酶表达来增加缓激肽水平。机械上,缓激肽通过B2R抑制Nrf2-xCT通路，引起肾脏氧化应激损伤。Icatibant的应用，B2R抑制剂，逆转Nrf2-xCT通路和氧化应激损伤的变化。最后,Icatibant在体内逆转了低温诱导的AKI。这一发现揭示了HCA后AKI的发病机制，并有助于为HCA后AKI患者提供治疗策略。
