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Antithrombin III Attenuates AKI Following Acute Severe Pancreatitis

Kong, Yiwei*; Yin, Jianyong*; Cheng, Dongsheng*; Lu, Zeyuan*; Wang, Niansong*; Wang, Feng*; Liang, Mingyu†,‡

doi: 10.1097/SHK.0000000000000946
Basic Science Aspects

Background: Antithrombin III (ATIII), the predominant coagulation factor inhibitor, possesses anti-inflammatory properties and exerts renoprotective effects on renal ischemia-reperfusion injury in animal models. However, the ATIII's protective effects of ATIII on acute kidney injury (AKI) following severe acute pancreatitis (SAP) need to be confirmed.

Methods: We assessed the association between ATIII activities and the incidence of AKI in patients with SAP, and explored therapeutic effects and potential mechanisms of ATIII on kidney injury in sodium taurocholate induced SAP rat model. Rats were intravenously injected with ATIII (500 μg/kg) before or after the induction of SAP.

Results: The results demonstrated ATIII did not attenuate pancreatic injury, but significantly ameliorate renal dysfunction and renal histological injury. ATIII administration alleviated renal inflammation response, oxidative stress, and cell apoptosis. Moreover, ATIII attenuated tumor necrosis factor α (TNFα)-stimulated intercellular cell adhesion molecule 1(ICAM-1) and monocyte chemotactic protein 1 (MCP-1) upregulation in cultured renal tubular epithelial cells.

Conclusion: ATIII appears to ameliorate SAP-induced kidney injury by inhibiting inflammation, oxidative stress, and apoptosis. ATIII supplementation may have a potential prophylactic and therapeutic effect on SAP induced AKI.

*Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin

Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin

Address reprint requests to Feng Wang, MD, PhD, 600 Yishan Road, Shanghai 200233, China. E-mail: zyzwq1030@hotmail.com

Received 23 February, 2017

Revised 14 March, 2017

Accepted 10 July, 2017

Drs YK, JY, and DC contributed to this work equally.

FW, JY, YK, and ML designed the experiments. JY, YK, DC, and ZL performed the experiments. FW, DC, and WN analyzed and interpreted the data. JY, DC, YK, and FW drafted the manuscript and ML revised the paper. All authors read and approved the final version of manuscript.

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

This work was sponsored by the National Natural Science Foundation of China (81570603), the New-100 talent Plan of Shanghai Jiao Tong University School of Medicine, Shanghai talents development fund (201350) and Shanghai Pujiang Talent Projects (15PJ1406700).

The authors report no conflicts of interest.

© 2018 by the Shock Society