Complement inhibition attenuates acute kidney injury after ischemia-reperfusion and limits progression to renal fibrosis in mice.
Complement inhibition attenuates acute kidney injury after ischemia-reperfusion and limits progression to renal fibrosis in mice.
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补体抑制作用会减弱局部缺血 - 再灌注后的急性肾脏损伤，并限制了小鼠肾纤维化的进展。
DOI：
10.1371/journal.pone.0183701
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Fernandez LA
中科院分区：
文献类型：
--
作者：
Danobeitia JS;Ziemelis M;Ma X;Zitur LJ;Zens T;Chlebeck PJ;Van Amersfoort ES;Fernandez LA
补体系统是先天免疫的重要组成部分，在缺血再灌注损伤（IRI）的发病机制中发挥着重要作用。在这项研究中，我们研究了人类 C1 抑制剂 (C1INH) 对 IRI 的早期炎症反应以及随后的小鼠纤维化进展的影响。我们评估了损伤后 90 天的结构损伤、肾功能、急性炎症反应、纤维化进展和总体生存率。与媒介物 (PBS) 治疗的动物相比，再灌注前接受 C1INH 的动物存活率显着提高，肾功能也更优越。 C1INH 预处理还可以防止急性 IL-6、CXCL1 和 MCP-1 上调、C5a 释放、C3b 沉积以及中性粒细胞和巨噬细胞渗入肾组织。与未治疗的对照相比，这种抗炎作用与 IRI 后 30 天和 90 天纤维化 α 平滑肌肌动蛋白、结蛋白和天狼皮红标记物表达的显着减少以及 TGF-β1 肾脏水平的降低相关。我们的研究结果表明，在缺血性损伤之前静脉注射 C1INH 可保护肾脏免受炎症损伤和随后的纤维化进展。我们的结论是，IRI 背景下的早期补体阻断是预防缺血性急性肾损伤后纤维化的有效策略。
The complement system is an essential component of innate immunity and plays a major role in the pathogenesis of ischemia-reperfusion injury (IRI). In this study, we investigated the impact of human C1-inhibitor (C1INH) on the early inflammatory response to IRI and the subsequent progression to fibrosis in mice. We evaluated structural damage, renal function, acute inflammatory response, progression to fibrosis and overall survival at 90-days post-injury. Animals receiving C1INH prior to reperfusion had a significant improvement in survival rate along with superior renal function when compared to vehicle (PBS) treated counterparts. Pre-treatment with C1INH also prevented acute IL-6, CXCL1 and MCP-1 up-regulation, C5a release, C3b deposition and infiltration by neutrophils and macrophages into renal tissue. This anti-inflammatory effect correlated with a significant reduction in the expression of markers of fibrosis alpha smooth muscle actin, desmin and picrosirius red at 30 and 90 days post-IRI and reduced renal levels of TGF-β1 when compared to untreated controls. Our findings indicate that intravenous delivery of C1INH prior to ischemic injury protects kidneys from inflammatory injury and subsequent progression to fibrosis. We conclude that early complement blockade in the context of IRI constitutes an effective strategy in the prevention of fibrosis after ischemic acute kidney injury.
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