Skip to main content
SpringerLink
Log in

Effect of penehyclidine hydrochloride on expressions of MAPK in mice with CLP-induced acute lung injury

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Penehyclidine hydrochloride (PHC) is a new anticholinergic drug. PHC has been shown to have a good curative effect for sepsis. Mitogen-activated protein kinase (MAPK) has recently been considered to play an important role in sepsis. In this study, the role of MAPK signal pathways in protective effects of PHC preconditioning on acute lung injury in cecal ligation and puncture (CLP)-induced sepsis was investigated. Healthy female mice were randomly divided into 4 groups: sham control, CLP, and 0.3 or 0.45 mg/kg PHC. At 12 h after surgery, arterial blood was drawn for blood gas analysis, and lung tissue samples were collected to examine pulmonary microvascular permeability, IL-6 levels and myeloperoxidase (MPO) activity. MAPK protein expressions were measured using western blot technique. Compared with sham control mice, acute lung injury was induced in CLP group, which was indicated by decreased PaO2/FiO2, increased pulmonary microvascular permeability, IL-6 levels and MPO activity. Furthermore, mice’ exposure to CLP induced the increased protein levels of MAPK. Treatment of 0.45 mg/kg PHC markedly improved PaO2/FiO2, decreased pulmonary microvascular permeability, IL-6 levels and MPO activity, and inhibited expressions of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK. Taken together, these results suggest that PHC ameliorated acute lung injury through the inhibition of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK activation in septic mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Muenzer JT, Davis CG, Dunne BS, Unsinger J, Dunne WM, Hotchkiss RS (2006) Pneumonia after cecal ligation and puncture: a clinically relevant “two-hit” model of sepsis. Shock 26:565–570

    Article  PubMed  Google Scholar 

  2. Ma X, Xu D, Ai Y, Ming G, Zhao S (2009) Fas inhibition attenuates lipopolysaccharide-induced apoptosis and cytokine release of rat type II alveolar epithelial cells. Mol Biol Rep. doi:10.1007/s11033-009-9876-9

  3. Xiaozhi Chen (2003) Penehyclidine hydrochloride. Central South Pharmacy 1:188–189

    Google Scholar 

  4. Han XY, Liu H, Liu CH, Wu B, Chen LF, Zhong BH, Liu KL (2005) Synthesis of the optical isomers of a new anticholinergic drug, penehyclidine hydrochloride (8018). Bioorg Med Chem Lett 15:1979–1982

    Article  CAS  PubMed  Google Scholar 

  5. Li A, Duan ML, Weng YB, Hu B (2006) Clinical study on penehyclidine hydrochloride on treatment of septic shock. J Emerg Med 15:742–744

    Google Scholar 

  6. Shen W, Gan J, Xu S, Jiang G, Wu H (2009) Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway. Pharmacol Res 60:296–302

    Article  CAS  PubMed  Google Scholar 

  7. Zhan J, Wang Y, Wang C, Li J, Zhang Z, Jia B (2007) Protective effects of penehyclidine hydrochloride on septic mice and its mechanism. Shock 28:727–732

    CAS  PubMed  Google Scholar 

  8. Ruimi N, Petrova RD, Agbaria R, Sussan S, Wasser SP, Reznick AZ, Mahajna J (2010) Inhibition of TNFalpha-induced iNOS expression in HSV-tk transduced 9L glioblastoma cell lines by Marasmius oreades substances through NF-kappaB- and MAPK-dependent mechanisms. Mol Biol Rep. doi:10.1007/s11033-010-0035-0

  9. Li Y, Du X, Li F, Deng Y, Yang Z, Wang Y, Pen Z, Wang Z, Yuan W, Zhu C, Wu X (2006) A novel zinc-finger protein ZNF436 suppresses transcriptional activities of AP-1 and SRE. Mol Biol Rep 33:287–294

    Article  CAS  PubMed  Google Scholar 

  10. Raman M, Chen W, Cobb MH (2007) Differential regulation and properties of MAPKs. Oncogene 26:3100–3112

    Article  CAS  PubMed  Google Scholar 

  11. Obata K, Yamanaka H, Kobayashi K, Dai Y, Mizushima T, Katsura H, Fukuoka T, Tokunaga A, Noguchi K (2004) Role of mitogen-activated protein kinase activation in injured and intact primary afferent neurons for mechanical and heat hypersensitivity after spinal nerve ligation. J Neurosci 24:l0211–10222

    Article  Google Scholar 

  12. Thirunavukkarasu C, Watkins SC, Gandhi CR (2006) Mechanisms of endotoxin-induced NO, IL-6, and TNF-alpha production in activated rat hepatic stellate cells: role of p38 MAPK. Hepatology 44:389–398

    Article  CAS  PubMed  Google Scholar 

  13. Ying B, Yang T, Song X, Hu X, Fan H, Lu X, Chen L, Cheng D, Wang T, Liu D, Xu D, Wei Y, Wen F (2009) Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways. Mol Biol Rep 36:1825–1832

    Article  CAS  PubMed  Google Scholar 

  14. Maniatis NA, Orfanos SE (2008) The endothelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care 14:22–30

    Article  PubMed  Google Scholar 

  15. Zongze Z, Jia Z, Chang C, Kai C, Yanlin W (2009) Protective effects of remifentanil on septic mice. Mol Biol Rep 37(6):2803–2808. doi:10.1007/s11033-009-9828-4

    Article  PubMed  Google Scholar 

  16. Krens SF, Spaink HP, Snaar-Jagalska BE (2006) Functions of the MAPK family in vertebrate-development. FEBS Lett 580:4984–4990

    Article  CAS  PubMed  Google Scholar 

  17. Nash SP, Heuertz RM (2005) Blockade of p38 map kinase inhibits complement-induced acute lung injury in a murine model. Int Immunopharmacol 5:1870–1880

    Article  CAS  PubMed  Google Scholar 

  18. Matthiesen S, Bahulayan A, Holz O, Racké K (2007) MAPK pathway mediates muscarinic receptor-induced human lung fibroblast proliferation. Life Sci 80:2259–2262

    Article  CAS  PubMed  Google Scholar 

  19. Kim JY, Yang MS, Oh CD, Kim KT, Ha MJ, Kang SS, Chun JS (1999) Signalling pathway leading to an activation of mitogen-activated protein kinase by stimulating M3 muscarinic receptor. Biochem J 337:275–280

    Article  CAS  PubMed  Google Scholar 

  20. Caulfield MP, Birdsall NJ (1998) International union of pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50:279–290

    CAS  PubMed  Google Scholar 

  21. Hamilton SE, Nathanson NM (2001) The M1 receptor is required for muscarinic activation of mitogen-activated protein (MAP) kinase in murine cerebral cortical neurons. J Biol Chem 276:15850–15853

    Article  CAS  PubMed  Google Scholar 

  22. Yagle K, Lu H, Guizzetti M, Möller T, Costa LG (2001) Activation of mitogen-activated protein kinase by muscarinic receptors in astroglial cells: role in DNA synthesis and effect of ethanol. Glia 35:111–120

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This stydy was supported by a grant from Hubei Provincial Health Department (No. 2005JX2C61).

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Zhongnan Hospital of Wuhan University, East-lake Road 169, Wuhan, 430071, Hubei, China

    Jia Zhan, Zongze Zhang, Chang Chen, Kai Chen & Yanlin Wang

  2. Department of Anesthesiology, Taihe Hospital, Yunyang medical college, Shiyan, People’s Republic of China

    Yongpan Liu

Authors
  1. Jia Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongpan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zongze Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kai Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yanlin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yanlin Wang.

Additional information

Jia Zhan and Yongpan Liu were co-authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhan, J., Liu, Y., Zhang, Z. et al. Effect of penehyclidine hydrochloride on expressions of MAPK in mice with CLP-induced acute lung injury. Mol Biol Rep 38, 1909–1914 (2011). https://doi.org/10.1007/s11033-010-0310-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0310-0

Keywords

Search

Navigation