Toll‑like receptor 4 contributes to acute kidney injury after cardiopulmonary resuscitation in mice

Zhang,Qingsong; Li,Gang; Xu,Li; Li,Qian; Wang,Qianyan; Zhang,Yue; Zhang,Qing; Sun,Peng

doi:10.3892/mmr.2016.5599

Toll‑like receptor 4 contributes to acute kidney injury after cardiopulmonary resuscitation in mice

Authors:
- Qingsong Zhang
- Gang Li
- Li Xu
- Qian Li
- Qianyan Wang
- Yue Zhang
- Qing Zhang
- Peng Sun
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Affiliations: Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Urology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Emergency, Wuhan First Hospital, Wuhan, Hubei 430022, P.R. China, Department of Anesthesia, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Endocrinology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: August 8, 2016 https://doi.org/10.3892/mmr.2016.5599
Pages: 2983-2990
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild‑type (C3H/HeN) and TLR4‑mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI). The expression of TLR4, intercellular adhesion molecule‑1 (ICAM‑1), myeloperoxidase (MPO) and growth‑regulated oncogene‑β (GRO‑β) in kidney tissues was detected. The results demonstrated that the levels of Scr and BUN increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted in increased expression of TLR4, ICAM‑1, GRO‑β and MPO in a CA‑duration dependent manner. However, there was decreased expression of ICAM‑1, GRO‑β and MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were resistant to AKI as demonstrated by the minor changes in renal histology and function following CPR. In conclusion, mice suffered from AKI after successful CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its downstream signaling events that promote neutrophil infiltration via ICAM‑1 and GRO‑β may be important in mediating inflammatory responses to renal injury after CPR.

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