Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2015; 21(15): 4555-4563
Published online Apr 21, 2015. doi: 10.3748/wjg.v21.i15.4555
H2S mitigates severe acute pancreatitis through the PI3K/AKT-NF-κB pathway in vivo
Chun-Yan Rao, Lan-Ying Fu, Chang-Lun Hu, Dai-Xing Chen, Tian Gan, Yi-Cheng Wang, Xiao-Yan Zhao
Chun-Yan Rao, Lan-Ying Fu, Dai-Xing Chen, Tian Gan, Xiao-Yan Zhao, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
Chang-Lun Hu, Yi-Cheng Wang, Department of Endocrinology, Chongqing Corps Hospital of Chinese People′s Armed Police Forces, Chongqing 40061, China
Author contributions: Rao CY and Zhao XY designed the study; Rao CY, Fu LY and Hu CL performed the study; Chen DX and Tian G performed statistical analysis; Rao CY and Fu LY wrote the paper; all authors contributed to the writing of the manuscript and interpretation of the data.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiao-Yan Zhao, Professor, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400037, China. zhaoxx@medmail.com.cn
Telephone: +86-23-68755604
Received: July 29, 2014
Peer-review started: July 31, 2014
First decision: August 27, 2014
Revised: September 20, 2014
Accepted: December 5, 2014
Article in press: December 8, 2014
Published online: April 21, 2015
Abstract

AIM: To study the effect of hydrogen sulfide (H2S) on severe acute pancreatitis (SAP) in a rat model.

METHODS: Sprague-Dawley (SD) rats were administered an intraperitoneal injection of saline containing 20% L-Arg (250 mg/100 g) hourly for over 2 h to induce SAP. The rats were treated with DL-propargylglycine (PAG, 50 mg/kg) or different dosages of NaHS (5 mg/kg, 10 mg/kg, 20 mg/kg or 100 mg/kg). PAG or NaHS was administered 1 h before induction of pancreatitis. Rats were sacrificed 24 h after the last L-Arg injection. Blood and pancreas tissues were collected.

RESULTS: The H2S and cystathionine-γ-lyase mRNA levels in SAP rats were significantly lower than those in the control group, and treatment with PAG further reduced the H2S level. Nevertheless, H2S was significantly increased after NaHS administration compared with the SAP group, and the degree of upregulation was associated with the NaHS dosage. NaHS reduced the levels of plasma amylase, interleukin-6 and myeloperoxidase in pancreatic tissue. NaHS suppressed the degradation of IκBα and the activity of nuclear factor-κB, as well as the phosphorylation of PI3K/AKT.

CONCLUSION: H2S plays an anti-inflammatory role in SAP in vivo.

Keywords: Severe acute pancreatitis, Hydrogen sulfide, Cystathionine-γ-lyase, Cytokine, Signaling pathway

Core tip: In this research, we provide wide-ranging dosages of exogenous H2S (NaHS), from 5 mg/kg to 100 mg/kg, to study the role of H2S in severe acute pancreatitis (SAP) in vivo, and finally found that the level of H2S was reduced in rat SAP models, suggesting that H2S donor NaHS reduced the inflammatory indices of SAP, by inhibiting PI3K/AKT phosphorylation and down-regulating IκBα degradation and nuclear factor-κB activity.