Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice
Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice
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DOI：
10.1152/ajprenal.00107.2011
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发表时间：
2011-10-01
影响因子：
4.2
通讯作者：
Faubel, Sarah
中科院分区：
文献类型：
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作者：
Andres-Hernando, Ana;Altmann, Christopher;Faubel, Sarah
[10] Andres-Hernando A，Altmann C，Ahuja N，Lanaspa MA，Nemenoff R，He Z，Ishimoto T，Simpson PA，Weiser-Evans MC，Bacalja J，Faubel S.脾切除加重小鼠缺血性急性肾损伤后的肺损伤。美国肾脏生理学杂志301：F907-F916，2011年。首次发表于2011年6月15日; doi：10.1152/ajprenal.00107.2011。急性肾损伤（阿基）患者血清促炎细胞因子增加，呼吸系统并发症发生率增加。本研究的目的是检查肾和肾外细胞因子产生对小鼠AKI介导的肺损伤的影响。对C57 B1/6小鼠进行假手术、脾切除术、缺血性阿基或伴有脾切除术的缺血性阿基，并检查肾、脾和肝细胞因子mRNA、血清细胞因子和肺损伤。在缺血阿基的6小时内，肾脏、脾脏和肝脏中的促炎细胞因子IL-6、CXCL 1、IL-1 β和TNF-α增加。由于脾促炎细胞因子增加，我们假设脾切除术可以保护AKI介导的肺损伤。相反，与单独阿基脾切除术导致血清IL-6增加和更严重的肺损伤，如通过增加的肺毛细血管渗漏、更高的肺髓过氧化物酶活性和更高的肺CXCL 1所判断的。与假手术相比，脾切除术本身与血清IL-6升高或肺损伤无关。为了研究促炎反应增加的机制，测定了抗炎细胞因子IL-10的脾脏产生，并且其显著上调。为了证实脾IL-10下调阿基的促炎反应，向患有阿基的脾切除小鼠施用IL-10，其降低血清IL-6并改善肺损伤。我们的数据表明，阿基在缺乏通过脾IL-10产生的反抗炎反应的情况下导致旺盛的促炎反应和肺损伤。
Andres-Hernando A, Altmann C, Ahuja N, Lanaspa MA, Nemenoff R, He Z, Ishimoto T, Simpson PA, Weiser-Evans MC, Bacalja J, Faubel S. Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice. Am J Physiol Renal Physiol 301: F907-F916, 2011. First published June 15, 2011; doi:10.1152/ajprenal.00107.2011.-Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1 beta, and TNF-alpha were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury.