Skip to main content
SpringerLink
Log in

Protective Effects and Mechanisms of Shenhua Tablet (肾华片) on Toll-Like Receptors in Rat Model of Renal Ischemia-Reperfusion Injury

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

Abstract

Objectives

To investigate the protective effects and potential mechanisms of Shenhua Tablet (肾华片, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI).

Methods

Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside (150 mg•kg-1•d-1), low- and high-dose SHT (1.5 and 3.0 g•kg-1•d-1, repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling, serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed; pathological damage were scored after periodic acid-Schiffstaining. TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) protein and mRNA expressions were detected by inmmunohistochemistry, Western blot and qPCR. Tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) protein expressions were detected by enzyme linked immunosorbent assay.

Results

Compared with the sham group, the model group exhibited severe change in renal function (Scr: 189.42±21.50, P<0.05), pathological damage (damage score: 4.50±0.55, P<0.05), and the expression levels of TLR2, TLR4, MyD88, TNF-α, IL-6 were significantly higher than other groups. Meanwhile, the levels of TLRs in model group showed upward tendency from 24 to 72 h, unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent, and, in addition to TLRs, presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model (P<0.05); in particular, the most significant mitigation of these changes was observed in the SHT-H group (P<0.05).

Conclusion

TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the MyD88-dependent signaling pathway and exhibit some dose dependence.

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. Li YW, Zhang Y, Zhang L, Li X, Yu JB, Zhang HT, et al. Protective effect of tea polyphenols on renal ischemia/ reperfusion injury via suppressing the activation of TLR4/ NF-kB p65 signal pathway. Gene 2014;542:46–51.

    Article  CAS  PubMed  Google Scholar 

  2. Moreth K, Frey H, Hubo M, Zengbrouwers J, Nastase MV, Hsieh TH, et al. Biglycan-triggered TLR-2-and TLR-4-signaling exacerbates the pathophysiology of ischemic acute kidney injury. Matrix Biol J Int Soc Matrix Biol 2014;35:143–151.

    Article  CAS  Google Scholar 

  3. Kusch A, Hoff U, Bubalo G, Zhu Y, Fechner M, Schmidtullrich R, et al. Novel signalling mechanisms and targets in renal ischaemia and reperfusion injury. Acta Physiol 2013;208:25–40.

    Article  CAS  Google Scholar 

  4. Wu H, Ma J, Wang P, Corpuz TM, Panchapakesan U, Wyburn KR, et al. Hmgb1 contributes to kidney ischemia reperfusion injury. J Am Society Nephrol Jasn 2010;21:1878–1890.

    Article  CAS  Google Scholar 

  5. Friedewald JJ, Rabb H. Inflammatory cells in ischemic acute renal failure. Kidney Int 2004;66:486–491.

    Article  PubMed  Google Scholar 

  6. Kim BS, Lim SW, Li C, Kim JS, Sun BK, Ahn KO, et al. Ischemia-reperfusion injury activates innate immunity in rat kidneys. Transplantation 2005;79:1370–1377.

    Article  PubMed  Google Scholar 

  7. Wolfs TG, Buurman WA, Van SA, De VB, Daemen MA, Hiemstra PS, et al. In vivo expression of Toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol 2002;168:1286–1293.

    Article  CAS  PubMed  Google Scholar 

  8. Wu H, Chen G, Wyburn KR, Yin J, Bertolino P, Eris JM, et al. TLR4 activation mediates kidney ischemia/reperfusion injury. J Clin Invest 2007;117:2847–2859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen XM, Chen YP, Chen J. Multicentered, randomized, controlled clinical trial on patients with IgA nephropathy of qi-yin deficiency syndrome type. Chin J Integr Tradit West Med (Chin) 2007;27:101–105.

    Google Scholar 

  10. Li JJ, Chen XM, Gu Y, Wei RB, Du J, Shi SZ, et al. Effect of compound Shenhua Tablet on macrophage migration inhibition factor in renal tissue of 5/6 nephrectomized rats. Chin J Integr Tradit West Med (Chin) 2005;25:150–153.

    Google Scholar 

  11. Yang Y, Wei RB, Zheng XY, Qiu Q, Cui SY, Yin Z, et al. Effects of compound Shenhua Tablet, on renal tubular Na+-K+-ATPase in rats with acute ischemic reperfusion injury. Chin J Integr Med 2014;20:200–208.

    Article  PubMed  Google Scholar 

  12. Daemen MA, van de Ven MW, Heineman E, Buurman WA. Involvement of endogenous interleukin-10 and tumor necrosis factor-alpha in renal ischemia-reperfusion injury. Transplantation 1999;67:792–800.

    Article  CAS  PubMed  Google Scholar 

  13. Daemen MA, van Veer C, Wolfs TG, Buurman WA. Ischemia/ reperfusion-induced IFN-gamma up-regulation: involvement of IL-12 and IL-18. J Immunol 1999;162:5506–5510.

    CAS  PubMed  Google Scholar 

  14. Yamada K, Miwa T, Liu J, Nangaku M, Song WC. Critical protection from renal ischemia reperfusion injury by CD55 and CD59. J Immunol 2004;172:3869–3875.

    Article  CAS  PubMed  Google Scholar 

  15. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-t method. Methods 2001;25:402–408.

    Article  CAS  Google Scholar 

  16. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol Jasn 2006;17:1503–1520.

    Article  CAS  PubMed  Google Scholar 

  17. Yano T, Nozaki Y, Kinoshita K, Hino S, Hirooka Y, Niki K, et al. The pathological role of IL-18Ra in renal ischemia/ reperfusion injury. Lab Invest 2015;95:78–91.

    Article  CAS  PubMed  Google Scholar 

  18. Shigeoka AA, Holscher TD, King AJ, Hall FW, Kiosses WB, Tobias PS, et al. TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways. J Immunol 2007;178:6252–6258.

    Article  CAS  PubMed  Google Scholar 

  19. Tsuboi N, Yoshikai Y, Matsuo S, Kikuchi T, Iwami K, Nagai Y, et al. Roles of toll-like receptors in c-c chemokine production by renal tubular epithelial cells. J Immunol 2002;169:2026–2033.

    Article  CAS  PubMed  Google Scholar 

  20. Wong ET, Tergaonkar V. Roles of NF-kappaB in health and disease: mechanisms and therapeutic potential. Clin Sci 2009;116:451–465.

    Article  CAS  PubMed  Google Scholar 

  21. Li M, Khan AM, Maderdrut JL, Simon EE, Batuman V. The effect of Pacap38 on MyD88-mediated signal transduction in ischemia-/hypoxia-induced acute kidney injury. Am J Nephrol 2010;32:522–532.

    Article  CAS  PubMed  Google Scholar 

  22. Lam W, Bussom S, Guan F, Jiang Z, Zhang W, Gullen EA, et al. The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Translat Med 2010;245:2841–2857.

    Google Scholar 

  23. Gong SG. Protection of amrinone against lung injury induced by ischemia/reperfusion in rats. Chin J Contemp Pediatr (Chin) 2007;9:233–236.

    CAS  Google Scholar 

  24. Zhang PJ, Jin C, Lang J. Effect of atractylodes macrocephalaon polysaccharides for reducing liver ischemia/reperfusion injury in rats after orthotopic liver autotransplantation. Chin J Integr Tradit West Med (Chin) 2010;30:1193–1196.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China

    Qing-ping Li, Ri-bao Wei, Xi Yang, Xiao-yong Zheng, Ting-yu Su, Meng-jie Huang, Zhong Yin & Xiang-mei Chen

Authors
  1. Qing-ping Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ri-bao Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-yong Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ting-yu Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Meng-jie Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhong Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiang-mei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ri-bao Wei.

Additional information

Supported by the National Sciences Foundation of China (Nos. 81273968, 81471027 and 81401160), Ministerial Project of the National Working Commission on Aging (No. QLB2014W002), and the Four Hundred Project of Chinese People's Liberation Army (PLA) General Hospital (No. YS201408)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Qp., Wei, Rb., Yang, X. et al. Protective Effects and Mechanisms of Shenhua Tablet (肾华片) on Toll-Like Receptors in Rat Model of Renal Ischemia-Reperfusion Injury. Chin. J. Integr. Med. 25, 37–44 (2019). https://doi.org/10.1007/s11655-017-2756-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-017-2756-6

Keywords

Search

Navigation