■急性肾损伤(AKI),心肺复苏(CPR)后的常见并发症,严重影响心脏骤停(CA)患者的预后。然而,关于复苏后AKI的研究有限.此外,已经证明N-乙酰半胱氨酸(N-AC)作为ROS清除剂,对全身和局部缺血再灌注损伤具有多器官保护作用。然而,尚无研究报道其对复苏后AKI的保护作用和潜在机制.本研究旨在阐明N-AC对复苏后AKI的保护作用,并探讨其潜在机制是否通过激活肾脏中的Nrf-2/HO-1通路介导。
■建立大鼠心脏骤停模型。所有动物都分为四组:假,control,N-AC,和ZnPP基团。除ZnPP组外,每组动物根据存活时间分为两个亚组:6和48h。N-AC,和ZnPP组进行心室纤颤(VF)的诱导,8分钟未治疗的VF和心肺复苏。肾功能指标,使用商业试剂盒检测。通过苏木精-伊红(HE)染色评估肾脏病理变化。使用相应的指标测量氧化应激和炎症反应。使用末端尿苷缺口末端标记(TUNEL)染色评估细胞凋亡,通过蛋白质印迹法测量与凋亡和Nrf-2/HO-1途径相关的蛋白质的表达。
■N-AC抑制复苏后AKI。我们观察到N-AC降低了肾功能紊乱的生物标志物水平;改善了肾脏病理改变;抑制了细胞凋亡,氧化应激,和炎症反应。此外,N-AC显著降低肾脏中ROS的产生。更重要的是,与对照组相比,N-AC进一步上调N-AC组核Nrf2和内源性HO-1的表达。然而,HO-1抑制剂锌原卟啉(ZnPP)预处理后,N-AC对复苏后AKI的保护作用显着逆转。
■N-AC减轻CA动物模型的肾功能障碍和延长生存期。N-AC通过激活Nrf-2/HO-1途径部分发挥有益的肾保护作用。总之,所有这些结果表明,N-AC作为一种常见的临床药物,可能具有改善患者心脏骤停结局的潜在临床效用。
UNASSIGNED: Acute kidney injury (AKI), the common complication after cardiopulmonary resuscitation (CPR), seriously affects the prognosis of cardiac arrest (CA) patients. However, there are limited studies on post-resuscitation AKI. In addition, it has been demonstrated that N-acetylcysteine (N-AC) as an ROS scavenger, has multiorgan-protective effects on systemic and regional ischaemia-reperfusion injuries. However, no studies have reported its protective effects against post-resuscitation AKI and potential mechanisms. This study aimed to clarify the protective effects of N-AC on post-resuscitation AKI and investigate whether its potential mechanism was mediated by activating Nrf-2/HO-1 pathway in the kidney.
UNASSIGNED: We established cardiac arrest models in rats. All animals were divided into four groups: the sham, control, N-AC, and ZnPP groups. Animals in each group except for the ZnPP group were assigned into two subgroups based on the survival time: 6 and 48 h. The rats in the control, N-AC, and ZnPP groups underwent induction of ventricular fibrillation (VF), 8 min untreated VF and cardiopulmonary resuscitation. Renal function indicators, were detected using commercial kits. Renal pathologic changes were assessed by haematoxylin-eosin (HE) staining. Oxidative stress and inflammatory responses were measured using the corresponding indicators. Apoptosis was evaluated using terminal uridine nick-end labeling (TUNEL) staining, and expression of proteins associated with apoptosis and the Nrf-2/HO-1 pathway was measured by western blotting.
UNASSIGNED: N-AC inhibited post-resuscitation AKI. We observed that N-AC reduced the levels of biomarkers of renal function derangement; improved renal pathological changes; and suppressed apoptosis, oxidative stress, and inflammatory response. Additionally, the production of ROS in the kidneys markedly decreased by N-AC. More importantly, compared with the control group, N-AC further upregulated the expression of nuclear Nrf2 and endogenous HO-1 in N-AC group. However, N-AC-determined protective effects on post-resuscitation AKI were markedly reversed after pretreatment of the HO-1 inhibitor zinc protoporphyrin (ZnPP).
UNASSIGNED: N-AC alleviated renal dysfunction and prolonged survival in animal models of CA. N-AC partially exerts beneficial renal protection via activation of the Nrf-2/HO-1 pathway. Altogether, all these findings indicated that N-AC as a common clinical agent, may have the potentially clinical utility to improve patients the outcomes in cardiac arrest.