Antithrombin III prevents progression of chronic kidney disease following experimental ischaemic-reperfusion injury.
Antithrombin III prevents progression of chronic kidney disease following experimental ischaemic-reperfusion injury.
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抗凝血酶 III 可预防实验性缺血再灌注损伤后慢性肾病的进展
DOI：
10.1111/jcmm.13261
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发表时间：
2017-12
影响因子：
5.3
通讯作者：
Liang M
中科院分区：
文献类型：
--
作者：
Yin J;Wang F;Kong Y;Wu R;Zhang G;Wang N;Wang L;Lu Z;Liang M
急性肾脏疾病（AKI）导致进展为慢性肾脏疾病（CKD）的风险增加。抗凝血酶III （ATIII）是一种具有抗炎特性的强效抗凝剂，我们之前报道过ATIII不足会加重大鼠肾缺血再灌注损伤（IRI）。在这项研究中，我们研究了两种不同AKI模型大鼠AKI - CKD过渡的特征。根据我们的观察，采用左IRI +右肾切除术（NX - IRI）来确定ATIII是否在预防AKI后CKD进展方面具有治疗作用。我们观察到，与假手术大鼠相比，NX - IRI在NX - IRI后5周导致了显著的功能和组织学损伤，而给药ATIII可以减轻这种损伤。此外，我们注意到ATIII给药可显著减少NX - IRI -诱导的间质纤维化。与未处理的NX - IRI大鼠相比，服用ATIII的大鼠肾脏中胶原- 1、α -平滑肌肌动蛋白和纤维连接蛋白的表达明显减少。此外，ATIII的有益作用还伴随着M1样巨噬细胞募集的减少和M1样巨噬细胞依赖的促炎细胞因子（如肿瘤坏死因子α、诱导型一氧化氮合酶和白细胞介素1β）的下调，表明ATIII通过抑制炎症阻止AKI - CKD的转变。总体而言，ATIII显示出作为预防AKI后CKD进展的治疗策略的潜力。
Acute kidney disease (AKI) leads to increased risk of progression to chronic kidney disease (CKD). Antithrombin III (ATIII) is a potent anticoagulant with anti‐inflammatory properties, and we previously reported that insufficiencies of ATIII exacerbated renal ischaemia‐reperfusion injury (IRI) in rats. In this study, we examined the characteristic of AKI‐CKD transition in rats with two distinct AKI models. Based on our observation, left IRI plus right nephrectomy (NX‐IRI) was used to determine whether ATIII had therapeutic effects in preventing CKD progression after AKI. It was observed that NX‐IRI resulted in significant functional and histological damage at 5 weeks after NX‐IRI compared with sham rats, which was mitigated by ATIII administration. Besides, we noticed that ATIII administration significantly reduced NX‐IRI‐induced interstitial fibrosis. Consistently, renal expression of collagen‐1, α‐smooth muscle actin and fibronectin were substantial diminished in ATIII‐administered rats compared with un‐treated NX‐IRI rats. Furthermore, the beneficial effects of ATIII were accompanied with decreased M1‐like macrophage recruitment and down‐regulation of M1‐like macrophage‐dependent pro‐inflammatory cytokines such as tumour necrosis factor α, inducible nitric oxide synthase and interleukin‐1β, indicating that ATIII prevented AKI‐CKD transition via inhibiting inflammation. Overall, ATIII shows potential as a therapeutic strategy for the prevention of CKD progression after AKI.
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影响因子：
19.6
作者：
Mehrotra P;Patel JB;Ivancic CM;Collett JA;Basile DP
通讯作者：
Basile DP
影响因子：
--
作者：
Brown JR;Rezaee ME;Marshall EJ;Matheny ME
通讯作者：
Matheny ME
影响因子：
13.6
作者：
Lech, Maciej;Groebmayr, Regina;Anders, Hans-Joachim
通讯作者：
Anders, Hans-Joachim
影响因子：
13.6
作者：
Ishani, Areef;Xue, Jay L.;Collins, Allan J.
通讯作者：
Collins, Allan J.
影响因子：
20.3
作者：
Dunzendorfer, S;Kaneider, N;Wiedermann, CJ
通讯作者：
Wiedermann, CJ