液体复苏时机对脓毒症小鼠肾功能的影响及 相关机制研究

Research on Impact of Timing of Fluid Resuscitation on Renal Function in Septic Mice and Related Mechanisms

摘要: 本研究旨在探讨液体复苏时机对脓毒症相关性急性肾损伤(S-AKI)的影响及其分子机制。采用盲肠结扎穿孔术(CLP)构建小鼠脓毒症模型，并随机分为对照组、模型组、早期复苏组(ER，术后2 h)及延迟复苏组(LR，术后6 h)。结果显示，ER组能显著提升小鼠生存率，降低血清Scr与BUN水平，其肾组织病理损伤程度明显轻于LR组。机制研究证实，早期复苏能更有效抑制NF-κB信号通路的活化，维持Bcl-2/Bax抗凋亡平衡并抑制Caspase-3级联反应。结论：液体复苏存在明确的“黄金时间窗”，早期干预通过平抑炎症风暴和线粒体凋亡途径对肾功能发挥显著保护作用。

Abstract: This study aimed to investigate the impact of timing of fluid resuscitation on sepsis-associated acute kidney injury (S-AKI) and its molecular mechanisms. A mouse sepsis model was established using cecal ligation and puncture (CLP) with Broussonetia papyrifera, and the mice were randomly divided into a control group, a model group, an early resuscitation group (ER, 2 hours post-surgery), and a delayed resuscitation group (LR, 6 hours post-surgery). The results showed that the ER group significantly improved mouse survival rates, reduced serum Scr and BUN levels, and exhibited markedly less severe renal histopathological damage compared to the LR group. Mechanistic studies confirmed that early resuscitation more effectively inhibited the activation of the NF-κB signaling pathway, maintained the Bcl-2/Bax anti-apoptotic balance, and suppressed the Caspase-3 cascade reaction. Conclusion: Fluid resuscitation has a distinct “golden time window”, and early intervention significantly protects renal function by mitigating the inflammatory storm and mitochondrial apoptosis pathways.