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Ligustrazine suppresses renal NMDAR1 and caspase-3 expressions in a mouse model of sepsis-associated acute kidney injury

  • Jing Ying
  • Jin WuEmail author
  • Yiwei Zhang
  • Yangyang Han
  • Xinger Qian
  • Qiuhong Yang
  • Yongjie Chen
  • Yijun Chen
  • Hao Zhu
Article
  • 43 Downloads

Abstract

Sepsis-associated acute kidney injury (AKI) is a life threatening condition with high morbidity and mortality. The pathogenesis of AKI is associated with apoptosis. In this study, we investigated the effects of ligustrazine (LGZ) on experimental sepsis-associated AKI in mice. Sepsis-associated AKI was induced in a mice model using cecal ligation and puncture (CLP) method. Mice were administered LGZ (10, 30, and 60 mg/kg) via tail vein injection 0.5 h before CLP surgery. Mice survival was evaluated. Renal water content was detected. Urine samples were collected for ELISA of Kim1. Kidneys were collected for nucleic acid analysis and histological examination. Pathological assessment was used to determine the effect of LGZ on sepsis-associated AKI. Caspase-3 expression in kidney was assessed by immunohistochemistry. Renal NMDAR1 level was also determined. Treatment of LGZ improved mice survival rate; the effect was significant when administered at a high LGZ dose (60 mg/kg). Renal water content of mice undergoing CLP was significantly reduced by LGZ treatment. Both middle-dose and high-dose LGZ treatments reduced urine Kim1 level in sepsis-associated AKI mice. The severity of AKI in septic mice was reduced by middle-dose and high-dose LGZ administration. Immunohistochemical analysis revealed decreased caspase-3 and NMDAR1 levels in the kidney following middle-dose and high-dose LGZ treatments. RT-PCR assay showed a significant reduction in NMDAR1 mRNA expression in the kidney of middle-dose and high-dose LGZ-treated mice. LGZ exhibited protective effects against sepsis-associated AKI in mice, possibly via downregulation of renal NMDAR1 expression and its anti-apoptotic action by inhibiting caspase-3.

Keywords

Ligustrazine Acute kidney injury Sepsis Apoptosis Caspase-3 NMDAR1 

Notes

Funding

This study was funded by Ningbo Natural Science Foundation (Grant Number 2017A610192).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethic approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. (Institutional Animal Care and Use Committee of Hangzhou Hibio Technology Co. Ltd., IACUC Protocol Number: HBFM3.68-2015).

Informed consent

Not applicable.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jing Ying
    • 1
  • Jin Wu
    • 1
    Email author
  • Yiwei Zhang
    • 1
  • Yangyang Han
    • 1
  • Xinger Qian
    • 1
  • Qiuhong Yang
    • 1
  • Yongjie Chen
    • 1
  • Yijun Chen
    • 1
  • Hao Zhu
    • 1
  1. 1.Department of AnesthesiologyNingbo First HospitalNingboChina

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