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Inhibitory Effect of Rhein on Renal Fibrosis in Diabetic Nephropathy Rats

대황산(大黃酸)의 당뇨병쥐 신장조직섬유화 억제 효과에 관한 실험연구

  • Zhao, Rongjie (Department of Pharmacology Mudanjiang Medical University) ;
  • Zhao, Zhenglin (Department of Biochemistry Mudanjiang Medical University) ;
  • Zhang, Jie (Department of Biochemistry Mudanjiang Medical University) ;
  • Liu, Hongfeng (Department of Biochemistry Mudanjiang Medical University) ;
  • Cui, Rongjun (Department of Biochemistry Mudanjiang Medical University) ;
  • Kim, Sang Chan (College of Oriental Medicine, Daegu Haany University) ;
  • Kim, Sun-Hyung (College of Oriental Medicine, Dongguk University)
  • 조용걸 (모단강의학원 약리학교실) ;
  • 조정림 (모단강의학원 생화학교실) ;
  • 장걸 (모단강의학원 생화학교실) ;
  • 류홍봉 (모단강의학원 생화학교실) ;
  • 최영군 (모단강의학원 생화학교실) ;
  • 김상찬 (대구한의대학교 방제학교실) ;
  • 김선형 (동국대학교 한의과대학)
  • Received : 2013.06.03
  • Accepted : 2013.06.10
  • Published : 2013.06.30

Abstract

Objectives : To investigate the therapeutic effect and underlying mechanisms of rhein on renal fibrosis in diabetic rats. Methods : Diabetic nephropathy (DN) was induced in adult Wistar rats via introperitoneal injection of streptozotocin (STZ) (20 mg/kg/d) for three consecutive days. Two days after the last dose of STZ, rhein was administered to the diabetic rats at a dose of 25 mg/kg or 50 mg/kg, twice a day by gavage, respectively. Following 28 days treatment with rhein, the plasma glucose and creatinine levels were measured, the renal levels of TGF-${\beta}1$ protein and mRNA were examined, and the fibronectin mRNA levels were also determined. Results : Rhein significantly inhibited the increased plasma glucose and creatinine levels of diabetic rats in a dose- and a time-dependent way. Immunohistochemical analysis showed both doses of rhein markedly attenuated elevated induction of renal TGF-${\beta}1$ protein expressions in diabetic rats. Additionally, the high dose of rhein improved both TGF-${\beta}1$ and fibronectin mRNA expressions, while the low dose of rhein only alleviated fibronectin mRNA expressions. Conclusions : Rhein can improve renal fibrosis in diabetic nephropathy rats, and which may be mediated through inhibition of the renal mRNA expressions of TGF-${\beta}1$ and fibronectin.

Keywords

References

  1. Munaka KR. Long-term complications of diabetes mellitus, part 1:retinopathy, nephropathy, neuropathy, Vet Clin North Am Small Anim Pract. 1995;25:715-30. https://doi.org/10.1016/S0195-5616(95)50064-6
  2. Nichols R. Complications and concurrent disease association with diabetes mellitus, Semin Vet Med Surg (Small Anim). 1997;12:263-7. https://doi.org/10.1016/S1096-2867(97)80019-9
  3. Eddy AA. Expression of genes that promote renal interstitial fibrosis in rats with proteinuria. Kidney Int. 1996;49:S49-S54.
  4. Ruoslahti E, Yamaguchi Y. Proteoglycans as modulators of growth factor activities. Cell, 1991;64:867-9. https://doi.org/10.1016/0092-8674(91)90308-L
  5. Eddy AA. Molecular insights into renal interstitial fibrosis. J Am Soc Nephrol. 1996;7:2495-508.
  6. Border WA, Noble NA. Transforming growth factor in tissue fibrosis. N Engl J Med. 1994;331:1286-92. https://doi.org/10.1056/NEJM199411103311907
  7. Flaumenhaft R, Abe M, Migntti P, Rifkin DB. Basic fibroblast growth factor-induced activation of latent transforming growth factor in endothelial cells: regulation of plasminogen activator activity. M J Cell Biol. 1992;118:901-9. https://doi.org/10.1083/jcb.118.4.901
  8. Okuda A, Languino LR, Ruoslahti E, Border WA. Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis: possible role in expansion of the mesangial extracellular matrix. J Clin Invest. 1990;86:453-62. https://doi.org/10.1172/JCI114731
  9. Sporn MB, Roberts AB. Transforming growth factor-beta : recent progress and new challenges. J Cell Biol. 1992;119:1017-21. https://doi.org/10.1083/jcb.119.5.1017
  10. Massague J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753-91. https://doi.org/10.1146/annurev.biochem.67.1.753
  11. Ziyadeh FN, Hoffman BB, Han DC, Iglesias-De La Cruz MC, Hong SW, Isono M, Chen S, McGowan TA, Sharma K. Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. Proc Natl Acad Sci USA. 2000;97:8015-20. https://doi.org/10.1073/pnas.120055097
  12. 郭嘯화, 劉志紅, 王建平 等. 大黃酸對NOD小鼠糖尿病腎病的治療作用관察. 腎臟病여透析腎移植雜志. 2002;11:11-6.
  13. 郭嘯화, 劉志紅, 彭艾 等. 大黃酸대2型糖尿病腎病大鼠療效관察. 中화腎臟病雜志. 2002;18:280-4.
  14. Guo XH, Liu ZH, Dai CS, Li H, Liu D, Li LS. Rhein inhibits cell hypertrophy and accumulation of extracellular matrix in renal tubular epithelial cells induced by transforming growth factor-${\beta}1$. Acta Pharmacol Sin. 2001;22:934-8.
  15. Mogyorosi A, Ziyadeh FN. GLUT1 and TGFbeta: the link between hyperglycaemia and diabetic nephropathy. Nephrol Dial Transp lant. 1999;14:2827-9. https://doi.org/10.1093/ndt/14.12.2827
  16. Brosius FC, Heilg CW. Glucose transporters in diabetic nephropathy. Pediatr Nephrol. 2005;20:447-51. https://doi.org/10.1007/s00467-004-1748-x
  17. Gilbert RE, Cox A, Wu LL, Allen TJ, Hulthen UL, Jerums G, Cooper ME. Expression of transforming growth Factor-beta1 and type IV collagen in the renal tubulointerstitium in experimental diabetes: effects of ACE inhibition. Diabetes. 1998;47:414-22. https://doi.org/10.2337/diabetes.47.3.414