Mechanism of the reversibility of chronic cyclosporine nephrotoxicity after drug withdrawal
- VernacularTitle:药物中断对慢性环孢素A肾毒性可逆性的机制研究
- Author:
Can LI
;
Ying CHEN
;
Mingyu HONG
- Publication Type:Journal Article
- Keywords:
Cyclosporine A;
Nephrotoxicity;
Osteopontin;
Transforming growth factor;
Drug withdrawal;
Tubulointerstitial fibrosis
- From:
Chinese Journal of Nephrology
1997;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of the reversibility of chronic cyclosporine (CsA) nephrotoxicity in rats after long-term drug withdrawal. Methods Chronic CsA nephrotoxicity was induced in Sprague-Dawley rats by administering CsA(15 mg . kg-1. d-1) for 5 weeks,and then the effect of drug withdraw for 5 and 10 weeks was observed. Body weight,systolic blood pressure,and renal function were monitored. In addition,renal histopathology(arteriolopathy,ED-1-positive cells,and tubulointerstitial fibrosis) and expression of osteopontin(OPN) and transforming growth factor(TGF) -?1 mRNA was examined. Results Compared with the control rats,CsA-treated rats showed loss of body weight,deterioration in renal function and development of typical histopathology. All of these above parameters were significantly reversed,meanwhile,the upregulation of OPN and TGF-?1 mRNA expression decreased significantly at 5th and 10th week after CsA withdrawal. Of note,the decreased OPN and TGF-?1 mRNA expression was positively correlated with the reduction in the tubulointerstitial fibrosis score. Conclusion The established chronic CsA nephrotoxicity is reversible after long-term CsA discontinuation,and the mechanism may be associated with the down-regulation of OPN and TGF-?1 mRNA expression.
