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Oxymatrine improves L-arginine-induced acute pancreatitis related intestinal injury via regulating AKT/NFkB and claudins signaling

  • Hui Zang
  • Zhiqiang Zhang
  • Qingfeng Liu
  • Huimin Xiao
  • Tian Sun
  • Enling Guo
  • Lankun Zhang
  • Bensong Gong
Original Research
  • 14 Downloads

Abstract

Oxymatrine (OMT) plays a significant role in chemical agents induced intestinal injury. However, its functional role in L-arginine (Arg) induced acute pancreatitis (AP) following intestinal injury and the corresponding molecular mechanism are unclear to our knowledge. We investigate OMT function in Arg induced AP following intestinal injury in vivo and vitro. OMT (4 mg/ml) decreased Arg (from 100 to 600 µM) induced IEC-6 cells growth in dose-dependent manner and inhibited Arg induced the increase of pAKT, bcl2, and the decrease of Bax. Meanwhile, OMT inhibited Arg (600 µM) induced the increase of pro-inflammatory cytokines TNF-a, IL-6, IL-1β, and NFkBp65 and the decrease of anti-inflammatory cytokine IL-10 expression. Moreover, the change of tight junction proteins claudins 1–4 expression induced by Arg was also reversed by OMT. Consistent with the results in vitro, OMT (50 mg/kg) inhibited Arg (250 mg/100 g) induced AP following intestinal injury in vivo. In detail, OMT resisted Arg induced inflammatory histology of both pancreas and intestine and inhibited Arg induced the change of pAKT, Bax, bcl2, TNF-a, IL-6, IL-1β, IL-10, NFkBp65, claudin 1–4 expression. Moreover, OMT inhibited Arg induced NFkBp65 and ICAM-1 expression in vivo by IHC. Oxymatrine improves Arg-induced acute pancreatitis following intestinal injury via inhibiting AKT/NFkB and claudins signaling.

Keywords

Oxymatrine L-arginine Acute pancreatitis Intestinal injury Inflammation Claudins 

Abbreviations

OMT

Oxymatrine

Arg

L-arginine

AP

Acute pancreatitis

qRT-PCR

Real-time PCR

WB

Western Blot

IHC

Immunohistochemistry

HE

hematoxylin-eosin

Notes

Acknowledgements

We thank for the Central Laboratory and General Laboratory of the First Hospital of China Medical University for technical supports. This work was supported by Natural Science Foundation from Liaoning (20170540540) and by the science and technology program from Shenyang (population and health special project, 17-230-9-36).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hui Zang
    • 1
    • 2
  • Zhiqiang Zhang
    • 1
    • 2
  • Qingfeng Liu
    • 1
    • 2
  • Huimin Xiao
    • 2
  • Tian Sun
    • 2
  • Enling Guo
    • 1
  • Lankun Zhang
    • 2
  • Bensong Gong
    • 1
    • 2
  1. 1.Department of General SurgeryThe People’s Hospital of Liaoning ProvinceShenyangChina
  2. 2.Department of General SurgeryThe People’s Hospital of China Medical UniversityShenyangChina

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