Skip to main content
Log in

Treatment of chronic dysfunction of transplantation kidney in rats —by tanshinone, lysimachiae combined with mycophenolate mofetil or cyclosporine alone

  • Published:
Chinese Journal of Integrated Traditional and Western Medicine Aims and scope Submit manuscript

Abstract

Objective: To evaluate the relationship between chronic kidney dysfunction after transplantation and chronic vascular rejection (CVR), and to evaluate the efficacy and safety of Tanshinone (Tan) and Herba Lysimachiae (Lys) combined with Mycophenolate Mofetil (MMF) to fight against CVR, and to reduce the incidence of chronic dysfunction in rat renal transplantation model.Methods: Sixty-five male SD rats as donors and sixty-five male Wistar rats as recipients were used. The recipients were divided into five Groups, including Group A: Lys + Cyclosporine A (CsA), Group B: Tan+CsA, Group C: MMF+CsA, Group D: CsA, and Group E: normal saline. Kidney function and morphological changes were assessed at 2, 4, and 6 weeks after transplantation. All sections of renal grafts were stained with monoclonal antibodies (McAB),. including major histocompability complex class II (OX-6), lymphocyte function antigen-1 (CDllb/CD18), intercellular adhesive molecular-1 (IA29), CD8+ (OX-8), and proliferation cell nuclear antigen (PCNA) (5A10, IgGlk) were used. Results:The two control groups developed typical chronic rejection episodes, and the histologic feature indication of kidney chronic rejection includes loss of renal units and presence of an obliteration arteriopathy involving large renal arteries. These were associated with serum levels of BUN and SCr increased and different degrees of glomerulosclerosis. Their mean survival time was lower than that of other groups. By contrast, serum levels of cytokine in control groups was significantly increased when compared with group B and C (P<0.05). Both group B and C had minimum changes in glomeruli and arteries, and expression levels of PCNA on the glomeruli and tubular cells were higher than those of other groups (P<0. 05). However, there was no significant difference (P>0.05) between group B and C.Conclusions: CVR may activate the risk of the factor responsible for the development of graft chronic dysfunction that causes slow, progressive destruction of the transplanted kidney. Tanshinone was extracted from Salvia miltiorrhiza and purified for use in medicine. Especially when Tanshinone combined with a low-dose of CsA, it may fight against the CVR by inhibiting cell infiltration, and improving microcirculation of the graft, and thus the incidence of CVR is reduced. It is suggested that Tanshinone can be applied to treat patients with chronic renal dysfunction when used in combination with a low-dose Cyclosporine.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hayry P, Aavik E, Savolainen H. Mechanisms of chronic rejection. Transplantation Proc 1999; 31(7A): 5–8.

    Article  CAS  Google Scholar 

  2. Kurokawa T, Takagi H. Mechanism and prevention of ischemia-reperfusion injury. Transplant Proc 1999; 31:1775 -17769.

    Article  PubMed  CAS  Google Scholar 

  3. Jerzy W, Kupiec W. Chronic allograft rejection. Current opinion in Organ Transplantation 1999;4:1 -2.

    Article  Google Scholar 

  4. Faber J, Lime SH, Morris PJ, et al. Renal transplantation in the rat: Details of technique. The Australian and New Zealand J Surgery 1971; 41 (1): 69–75.

    Google Scholar 

  5. Solez RA, Axelsen B, Hallgrimur BK, et al. International standardization of criteria for the histology diagnosis of renal allograft rejection: The Banff working classification of kidney transplant pathology. Kidney Int 1993;44(suppl):411–422.

    Article  PubMed  CAS  Google Scholar 

  6. Sheng H. A method for studies Immunohistochemistry quantification. J Chin Histochemistry and Cellular Chemistry 1995;4(1): 59–61.

    Google Scholar 

  7. Yang XY. Measure the levels of PCNA expression — different methods affects. Chin J Pathol 1993; 22(2): 74–76.

    CAS  Google Scholar 

  8. Foggy ML. Chronic rejection-graft arteriosclerosis. Trans- plantation Proc 1990;22(1): 119–122.

    Google Scholar 

  9. Dimness E, Fellstrom B, Larsson E, et al. Can chronic vas- cular rejection of a renal transplant be predicted? Transplant Proc 1995;27(1):881–883.

    Google Scholar 

  10. Fellstrom B, Backman U, Larsson E, et al. Are their markers to initate treatment of chronic rejection? Transplant Proc 1999; 31: 1796–1798.

    Article  PubMed  CAS  Google Scholar 

  11. Briscoe DM, Ganz PT, Stephen I, et al. The problem of chronic rejection: Influence of leukocyte-endothelial interactions. Kidney Int 1997;51(suppl 58):22–27.

    Google Scholar 

  12. Manikkam SA, Morris RE, Strom TB. Immunosuppressants: Cellular and molecular mechanisms of action. Am J Kidney Dis 1996; 28(2): 159–172.

    Article  Google Scholar 

  13. Huang XL, Shen WL, LI YP, et al. Expression of ICAM-1 and LFA-1 molecules in relation to renal allograft rejection in rats. Chin Med Sci J 1999; 14(3): 163–166.

    PubMed  Google Scholar 

  14. Huang XL, Shen WL, Zhou ZQ. Medicine S inhibits class II MHC expression of intra-graft kidney in rats. J West Chin Univ of Med 1997;28(2):204–208.

    CAS  Google Scholar 

  15. Huang XL, Shen XL, LI YP, et al. Chinese drug S and B inhibited expression of ICAM-1 and LFA-1 in renal allografts during rejection. Chin J Nephrology 1998,14(1): 43–46.

    CAS  Google Scholar 

  16. Lemstrom KL, Koskinen PT, Hayry PA. Molecular mechanisms of chronic renal allograft rejection. Kidney Int 1995; 48(suppl 52):2–10.

    Google Scholar 

  17. Park SK, Kang MJ, Kon GY. Renal tubule regeneration after ischemic injury is coupled to the up-regulation and activation of cyclins and cyclin dependent kinases. Kidney Int 1997;52:706–714.

    Article  PubMed  CAS  Google Scholar 

  18. Kurokawa T, Takagi H. Mechanism and prevention of ischemia-reperfusion injury. Transplant Proc 1999; 31:1775 -1779.

    Article  PubMed  CAS  Google Scholar 

  19. Gohra HE, Thomas O, Mcdonald EA, et al. Endothelial loss and regeneration in a model of transplant arteriosclerosis. Transplantation 1995; 60(l):96–102.

    Article  PubMed  CAS  Google Scholar 

  20. Jin HM, GU ZL, Wang XH, et al. Clinical application of Salvia preparation and its therapeutical principle of activating blood circulation to remove stasis. Chin Med J 1978; 3:180–185.

    Google Scholar 

  21. CUI H, WANG X, ZHONG ZH, et al. Effect of Salvia to the (methyl-3H) thymidine nucleotide incorporation to cultured hepatocyte in vitro. Pharmacy Bulletin 1987;22(9): 535.

    Google Scholar 

  22. CHEN LZ, ZHOU BL, WU ZQ, et al. Preliminary observation on Salvia in adjusting experimental hepatic microcirculatory disturbance. CJIM 1988;8(3): 161–165.

    Google Scholar 

  23. Forber JS, Orosz CG, Rose ML, et al. Can graft endothelial cells initiate a host antigraft immune response? Transplantation 1996;61(3): 343–349.

    Article  Google Scholar 

  24. Foung RA, Burdman EA, Johnson RJ, et al. Cyclosporine, an induced arteriolopathy in a rat model of chronic cyclosporine nephropathy. Kidney Int 1996;49(3): 1141–1151.

    Google Scholar 

  25. Maria JG, Biol SD, Carla IJ, et al. Cyclosporine enhances leukocyte adhesion to vascular endothelium under physiologic flow conditions. Am J Kidney Dis 1996; 28(1): 23–31.

    Article  Google Scholar 

  26. Johnson HA, Bond VP, A method of labeling tissues with tritiated thymidine in vitro and its use in comparing rates of cellular proliferation duct epithelium of the human breast. Cancer 1961; 14:693–642.

    Article  Google Scholar 

  27. Linden MD, Torres FX, Kubus J, et al. Clinical application of morphologic and immunocyto-chemical assessments of proliferation. Am J Clin Pathol 1992;97(suppl I):S4-S8.

    PubMed  CAS  Google Scholar 

  28. Shankcan SJ. Cell-cycle control and renal disease. Kidney Int 1997:52:294–308.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by the Sciences Foundation of the Ministry of Health Grants (No. C 0103)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xiaolun, H., Wenlu, S., Guihua, C. et al. Treatment of chronic dysfunction of transplantation kidney in rats —by tanshinone, lysimachiae combined with mycophenolate mofetil or cyclosporine alone. CJIM 6, 208–213 (2000). https://doi.org/10.1007/BF02950930

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02950930

Key Words

Navigation