Skip to main content
SpringerLink
Log in

Protective effect of sodium tanshinone IIA sulfonate on injury of small intestine in rats with sepsis and its mechanism

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To explore the protective effect of sodium tanshinone IIA sulfonate (STS) on small: intestine injury in rats with sepsis and its possible mechanism.

Methods

According to a random number table, 24 Tats were randomly divided into 3 groups: sham operation group (sham group), sepsis model group (model group) and STS treatment group (STS group), with 8 Tats in each group. A rat model of sepsis was induced by cecal ligation and puncture (CLP) for 5 h. STS (1 mg/kg) was slowly injected through the right external jugular vein after CLP. The histopathologic changes in the intestine tissue were observed under a light microscope, and the intestinal epithelial cell apoptosis was evaluated by terminal deoxynucleoddyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. The expressions of Bcl-2, Bax and nuclear factor κB (NF-κB) p65 in the intestinal tissue was determined by Western blot. The levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the intestinal tissue were determined using enzyme-linked immuno-sorbent assay (ELISA).

Results

Obvious injuries were observed in the intestinal tissue in the CLP group compared with the sham group. The expression of NF-κB p65 and the levels of TNF-α and IL-6 were up-regulated after CLP, the apoptosis of intestinal epithelial cells was increased after CLP, and the ratio of Bcl-2 to Bax was decreased. STS post-treatment could attenuate the injury on the intestinal tissue induced by CLP, decrease the apoptosis of intestinal treatment epithelial cells and the levels of NF-κB p65, TNF-α and IL-6, and increase the ratio of Bcl-2 to Bax.

Conclusion

STS can protect the small intestine in rats with sepsis, and the mechanism may be associated with the inhibition of intestinal epithelial apoptosis and the reduction of activation of inflammatory cytokines.

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

Similar content being viewed by others

References

  1. Abraham E, Matthay MA, Dinarello CA, Vincent JL, Cohen J, Opal SM, et al. Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory dustress syndrome: time for a reevaluation. Crit Care Med 2000;28:232–235.

    Article  PubMed  CAS  Google Scholar 

  2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303–1310.

    Article  PubMed  CAS  Google Scholar 

  3. Dyson A, Singer M. Animal models of sepsis: why does preclinical efficacy fail to translate to the clinical setting? Crit Care Med 2009;37:S30–S37.

    Article  PubMed  Google Scholar 

  4. Poli-de-Figueiredo LF, Garrido AG, Nakagawa N, Sannomiva P. Experimental models of sepsis and their clinical relevance. Shock 2008;30(Suppl 1):53–59.

    Article  PubMed  CAS  Google Scholar 

  5. Liu SF, Malik AB. NF-κB activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol 2006;290:L622–L645.

    Article  PubMed  CAS  Google Scholar 

  6. Abraham E. Nuclear factor-κB and its role in sepsis-associated organ failure. Infect Dis 2003;187(Suppl 2): s364–s369.

    Article  CAS  Google Scholar 

  7. Liu F, Zheng Z. The mechanisms of Radix salviae miltiorrhizae in prevention of left ventricular hypertrophy in spontaneously hypertensive rats. Chin J Emerg Med (Chin) 2004;13:322–324.

    Google Scholar 

  8. Li W, Li J, Ashok M, Wu R, Chen D, Yang L, et al. A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1. J Immunol 2007;178:3856–3864.

    PubMed  CAS  Google Scholar 

  9. Xu Y, Feng D, Wang Y, Lin S, Xu L. Sodium tanshinone IIA sulfonate protects mice from ConA-induced hepatitis via inhibiting NF-kappaB and IFN-gamma/STAT1 pathways. J Clin Immunol 2008;28:512–519.

    Article  PubMed  CAS  Google Scholar 

  10. Yang R, Liu A, Ma X, Li L, Su D, Liu J. Sodium tanshinone IIA sulfonate protects cardiomyocytes against oxidative stress-mediated apoptosis through inhibiting JNK activation. J Cardiovasc Pharmacol 2008;51:396–401.

    Article  PubMed  CAS  Google Scholar 

  11. Yao YM, Wang SB, Xian LM, Zhai XZ, Dong N, Yu Y, et al. The potential mechanism on signal transduction pathway in regulation of mRNA expression of high mobility group box-1 protein in septic rats. Chin J Surg 2006;44:916–920.

    PubMed  Google Scholar 

  12. Kiernan JA. Histological and histochemical methods: theory and practice. 4th ed. Bloxham, UK: Scion; 2008.

    Google Scholar 

  13. Kruger NJ. The Bradford method for protein quantitation. In: Walker JM, ed. The protein protocols handbook. Hatfield UK: University of Herfordshire; 2002:15–21.

    Chapter  Google Scholar 

  14. Nieuwenhuijzen GA, Goris RJ. The gut: the “motor” of multiple organ dysfunction syndrome? Curr Opin Clin Nutr Metab Care 1999;2:399–404.

    Article  PubMed  CAS  Google Scholar 

  15. Wang J, Qiao LF, Yang GT. Role of Shenfu Injection in rats with systemic inflammatory response syndrome. Chin J Integr Med 2008;14:51–55.

    Article  PubMed  Google Scholar 

  16. Kim PK, Deutschman CS. Inflammatory responses and mediators. Surg Clin North Am 2000;80:885–894.

    Article  PubMed  CAS  Google Scholar 

  17. Hattori Y, Takano KI, Teramae H, Yamamoto S, Yokoo H, Matsuda N. Insights into sepsis therapeutic design based on the apoptotic death pathway. J Pharmacol Sci 2010;114:354–365.

    Article  PubMed  CAS  Google Scholar 

  18. Dutta J, Fan Y, Gupta N, Fan G, Gélinas C. Current insights into the regulation of programmed cell death by NF-kappaB. Oncogene 2006; 25:6800–6816.

    Article  PubMed  CAS  Google Scholar 

  19. Oberholzer C, Oberholzer A, Clare-Salzler M, Moldawer LL. Apoptosis in sepsis: a new target for therapeutic exploration. FASEB J 2001;15:879–892.

    Article  PubMed  CAS  Google Scholar 

  20. Lang JD, Matute-Bello G. Lymphocytes, apoptosis and sepsis: making the jump from mice to humans. Crit Care 2009;13:109.

    Article  PubMed  Google Scholar 

  21. Coopersmith CM, Chang KC, Swanson PE, Tinsley KW, Stromberq PE, Buchman TG, et al. Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice. Crit Care Med 2002;30:195–201.

    Article  PubMed  CAS  Google Scholar 

  22. Perl M, Chung CS, Perl U, Lomas-Neira J, de Paepe M, Cioffi WG, et al. Fas-induced pulmonary apoptosis and inflammation during indirect acute lung injury. Am J Respir Crit Care Med 2007;176:591–601.

    Article  PubMed  CAS  Google Scholar 

  23. Matsuda N, Hattori Y. Vascular biology in sepsis: pathophysiological and therapeutic significance of vascular function. J Smooth Muscle Res 2007;43:117–137.

    Article  PubMed  Google Scholar 

  24. Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE. Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T-and B-cell-deficient mice. Crit Care Med 1997;25:1298–1307.

    Article  PubMed  CAS  Google Scholar 

  25. Zhu W, Lu Q, Chen HW, Zhong Q, Yang GT. Effect of pentoxifylline on the expression of HSP70, NF-κB and apoptosis in intestinal tissues of rats with sepsis. Acta Med Univ Sci Technol Huazhong 2010;39:346–349.

    CAS  Google Scholar 

  26. Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci 2009;122:437–441.

    Article  PubMed  CAS  Google Scholar 

  27. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998;281:1309–1312.

    Article  PubMed  CAS  Google Scholar 

  28. Martin S, Toquet C, Oliver L, Cartron PF, Perrin P, Meflah K, et al. Expression of Bcl-2, Bax and Bcl-xL in human gliomas: a reappraisal. J Neurooncol 2001;52:129–139.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Emergency Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Wei Zhu  (祝 伟), Hua-wen Chen  (陈华文), Jun Feng  (冯 俊), Lei Wan  (万 磊) & Dai-xing Zhou  (周代星)

  2. Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Qing Lu  (吕 青)

Authors
  1. Wei Zhu  (祝 伟)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing Lu  (吕 青)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hua-wen Chen  (陈华文)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Feng  (冯 俊)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Wan  (万 磊)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dai-xing Zhou  (周代星)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Zhu  (祝 伟).

Additional information

Supported by a Grant from Hubei Province Science and Technique Foundation (No. 2009CDB371)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, W., Lu, Q., Chen, Hw. et al. Protective effect of sodium tanshinone IIA sulfonate on injury of small intestine in rats with sepsis and its mechanism. Chin. J. Integr. Med. 18, 496–501 (2012). https://doi.org/10.1007/s11655-011-0942-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-011-0942-5

Keywords

Search

Navigation