Liu Jiao, Abdel-Razek Osama, Liu Zhiyong, Hu Fengqi, Zhou Qingshan, Cooney Robert N, Wang Guirong
*Department of Surgery, SUNY Upstate Medical University, Syracuse, New York; †Department of Critical Care Medicine, Wuhan University, Renmin Hospital, Wuhan, Hubei Province, People's Republic of China.
Shock. 2015 Jan;43(1):31-8. doi: 10.1097/SHK.0000000000000270.
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. Twenty-four hours after CLP, kidney injury was more severe, renal function was decreased, and blood creatinine and blood urea nitrogen were higher in septic SP-A/SP-D KO mice (P < 0.05, versus septic WT mice). Kidney edema and vascular permeability were increased in septic SP-A/SP-D KO mice (P < 0.01, versus septic WT mice). Apoptotic cells increased significantly (P < 0.01) in the kidney of septic SP-A/SP-D KO mice compared with 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, versus septic WT mice). Furthermore, levels of nuclear factor κB and phosphorylated IκB-α increased significantly in the kidney of septic SP-A/SP-D KO mice compared with 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.
脓毒症是急性肾损伤（AKI）的主要病因，发病率和死亡率很高。表面活性蛋白A和D（SP-A、SP-D）在宿主防御中起关键作用，并在感染期间调节炎症。最近的研究表明SP-A和SP-D在肾脏中表达。本研究探讨SP-A和SP-D在脓毒症诱导的AKI发病机制中的作用。野生型（WT）和SP-A/SP-D双敲除（KO）C57BL/6小鼠接受盲肠结扎和穿刺（CLP）或假手术治疗。在CLP后6小时和24小时对脓毒症小鼠的肾脏损伤进行组织学、细胞和分子指标研究。CLP后24小时，脓毒症SP-A/SP-D KO小鼠的肾脏损伤更严重，肾功能下降，血肌酐和血尿素氮更高（P<0.05，与脓毒症WT小鼠相比）。脓毒症SP-A/SP-D KO小鼠的肾脏水肿和血管通透性增加（P<0.01，与脓毒症WT小鼠相比）。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著增加（P<0.01）。分子分析显示，脓毒症SP-A/SP-D KO小鼠肾脏中凋亡抑制因子Bcl-2水平较低，凋亡生物标志物半胱天冬酶3水平较高（P<0.01，与脓毒症WT小鼠相比）。此外，与脓毒症WT小鼠相比，脓毒症SP-A/SP-D KO小鼠肾脏中核因子κB和磷酸化IκB-α水平显著升高，表明SP-A/SP-D KO小鼠对脓毒症有更明显的炎症反应。我们得出结论，SP-A和SP-D通过调节脓毒症诱导的AKI中的炎症和凋亡来减轻肾脏损伤。
