Role of surfactant proteins A and D in sepsis-induced acute kidney injury.
Role of surfactant proteins A and D in sepsis-induced acute kidney injury.
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DOI：
10.1097/shk.0000000000000270
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Wang G
中科院分区：
文献类型：
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作者：
Liu J;Abdel-Razek O;Liu Z;Hu F;Zhou Q;Cooney RN;Wang G
脓毒症是急性肾损伤（AKI）的主要原因，发病率和死亡率很高。表面活性蛋白 A 和 D (SP-A、SP-D) 在宿主防御和感染过程中调节炎症中发挥着关键作用。最近的研究表明 SP-A 和 SP-D 在肾脏中表达。目前的研究探讨了 SP-A 和 SP-D 在脓毒症诱发的 AKI 发病机制中的作用。通过盲肠结扎穿刺 (CLP) 或假手术治疗野生型 (WT) 和 SP-A/SP-D 双敲除 (KO) C57BL/6 小鼠。 CLP 后 6 小时和 24 小时对脓毒症小鼠肾损伤的组织学、细胞和分子指标进行了研究。 CLP后24小时，脓毒症SP-A/SP-D KO小鼠肾损伤更严重，肾功能下降，血肌酐和BUN更高（与脓毒症WT小鼠相比，p<0.05）。脓毒症 SP-A/SP-D KO 小鼠的肾水肿和血管通透性增加（与脓毒症 WT 小鼠相比，p<0.01）。与脓毒症 WT 小鼠相比，脓毒症 SP-A/SP-D KO 小鼠肾脏中的凋亡细胞显着增加 (p<0.01)。分子分析显示，脓毒症 SP-A/SP-D KO 小鼠肾脏中 Bcl-2（细胞凋亡抑制剂）水平较低，caspase-3（细胞凋亡生物标志物）水平较高（与脓毒症 WT 小鼠相比，p<0.01）。此外，脓毒症 SP-A/SP-D KO 小鼠肾脏中 NF-κB 和磷酸化 IκB-α 的水平显着高于脓毒症 WT 小鼠，表明 SP-A/SP-D KO 小鼠对脓毒症有更明显的炎症反应。我们得出的结论是，SP-A 和 SP-D 通过调节脓毒症诱导的 AKI 中的炎症和细胞凋亡来减轻肾损伤。
Sepsis is a major cause of acute kidney injury (AKI) with high rates of morbidity and mortality. Surfactant proteins A and D (SP-A, SP-D) play a critical role in host defense and regulate inflammation during infection. Recent studies indicate SP-A and SP-D are expressed in the kidney. The current study examines the role of SP-A and SP-D in the pathogenesis of sepsis-induced AKI. Wild-type (WT) and SP-A/SP-D double knockout (KO) C57BL/6 mice were treated by cecal ligation and puncture (CLP) or sham surgery. Histological, cellular and molecular indices of kidney injury were investigated in septic mice 6 and 24 h after CLP. 24 h post-CLP, kidney injury was more severe, renal function was decreased, blood creatinine and BUN were higher in septic SP-A/SP-D KO mice (p<0.05, vs septic WT mice). Kidney edema and vascular permeability were increased in septic SP-A/SP-D KO mice (p<0.01, vs septic WT mice). Apoptotic cells increased significantly (p<0.01) in the kidney of septic SP-A/SP-D KO mice compared to septic WT mice. Molecular analysis revealed levels of Bcl-2 (an inhibitor of apoptosis) were lower and levels of caspase-3 (a biomarker of apoptosis) were higher in the kidney of septic SP-A/SP-D KO mice (p<0.01, vs septic WT mice). Furthermore, levels of NF-κB and phosphorylated IκB-α increased significantly in the kidney of septic SP-A/SP-D KO mice than septic WT mice, suggesting SP-A/SP-D KO mice have a more pronounced inflammatory response to sepsis. We conclude SP-A and SP-D attenuate kidney injury by modulating inflammation and apoptosis in sepsis-induced AKI.