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Apoptosis

, Volume 18, Issue 1, pp 28–42 | Cite as

Inhibition of hydrogen sulfide synthesis provides protection for severe acute pancreatitis rats via apoptosis pathway

  • Gang Wang
  • Bing Han
  • Haoxin Zhou
  • Linfeng Wu
  • Yongwei Wang
  • Guang Jia
  • Jiachen Lv
  • Zhuoxin Cheng
  • Shangha Pan
  • Ji Liu
  • Yinan Zhou
  • Bei SunEmail author
Original Paper

Abstract

We aimed to investigate the relationship between the synthesis of hydrogen sulfide (H2S) and the pancreatic acinar cell apoptosis in severe acute pancreatitis (SAP) rats, as well as analyse the potential apoptotic pathway involved in this process. Sixty rats had been equally divided into four groups: sham, SAP, SAP + sodium hydrosulfide (NaHS) and SAP + DL-propargylglycine (PAG). 24 h after SAP induction, all surviving animals of each group were sacrificed to collect blood and tissue samples for the following measurements: the level of serum H2S as well as the levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), H2S synthesizing activity, CSE mRNA and protein expression, maleic dialdehyde (MDA) and myeloperoxidase (MPO) activity, the expression of Bax, Bcl-2, caspase-3, -8 and -9, the release of cytochrome c and the activation of nuclear factor-kappa B (NF-κB), ERK1/2, JNK1/2 and p38 in pancreas. Furthermore, in situ detection of cell apoptosis was examined and the severity of pancreatic damage was analyzed by pathological grading and scoring. Results Significant differences in every index except IL-10 had been found between the SAP, NaHS and PAG groups (P < 0.05). Treatment with PAG obviously induced the pancreatic acinar cell apoptosis as well as improved all the pathological changes and inflammatory parameters. In contrast, administration of NaHS significantly attenuated apoptosis in the pancreas and aggravated the severity of pancreatic damage. Moreover, the expressions of caspase-3, -8, -9 and the release of cytochrome c were all increased in the apoptotic cells, and the activity of NF-κB as well as the phosphorylation of ERK1/2, JNK1/2 and p38 decreased accompanying with the reduction of the serum H2S level. H2S plays a pivotal role in the regulation of pancreatic acinar cell apoptosis in SAP rats. The present results showed that inhibition of H2S synthesis provided protection for SAP rats via inducing acinar cell apoptosis. This process acted through both extrinsic and intrinsic apoptotic pathways, and may be regulated by reducing the activity of NF-κB.

Keywords

Severe acute pancreatitis Hydrogen sulfide Apoptosis Mitochondrial pathway Death receptor pathway NF-κB 

Notes

Acknowledgments

This paper was supported by grants from the National Natural Scientific Foundation of China (No: 81170431, 81100314, 81101799, 30901437), Postdoctoral Science Foundation of China (No: 2012M511512), Youth Science Foundation of Heilongjiang Province (No: QC2011C036), Postdoctoral Science Foundation of Heilongjiang Provincial Government (No: 90857), Natural Scientific Foundation of Heilongjiang Province (No: D201152) and Research Fund of the First Affiliated Hospital of Harbin Medical University (No: 2009B03).

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Gang Wang
    • 1
  • Bing Han
    • 1
  • Haoxin Zhou
    • 1
  • Linfeng Wu
    • 1
  • Yongwei Wang
    • 1
  • Guang Jia
    • 1
  • Jiachen Lv
    • 1
  • Zhuoxin Cheng
    • 1
  • Shangha Pan
    • 2
  • Ji Liu
    • 1
  • Yinan Zhou
    • 1
  • Bei Sun
    • 1
    Email author
  1. 1.Department of Pancreatic and Biliary SurgeryFirst Affiliated Hospital of Harbin Medical University HarbinChina
  2. 2.Central LaboratoryFirst Affiliated Hospital of Harbin Medical UniversityHarbinChina

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