Objective To evaluate the effect of inhibition of transforming growth factor-beta 1 (TGF-?1) expression by liposome-mediated antisense oligonucleotides on chronic nephrotoxicity induced by cyclos-porin A in rats. Methods Rats were on low salt diet and CsA was administered once every day by intraper-itoneal injection (15 mg/kg every day) for 4 weeks. Antisense oligodeoxynucleotides for TGF-?1 were introduced into the nephritic kidney by liposome-mediated gene transfer method to inhibit the overproduction of TGF-?1. Results Under the condition of low salt diet, a rat model of CsA-induced nephrotoxicity was established. The changes of level of serum creatinine and characteristic histopathology of proximal tubular injury and tubulointerstitial fibrosis were observed. In the liposome-mediated AODN rats, the expression of TGF-?1 mRNA was decreased by RT-PCR (P

Objective To investigate the effects of substituting tacrolimus (FK506) for cyclosporine (CsA) on delaying the pace of renal dysfunction in patients with biopsy-proven chronic allograft nephropathy (CAN) and the molecular mechanism of the therapy.Methods From January, 1999 to May, 2002, 93 renal transplant recipients with declining graft function and biopsy-proven CAN (Grade Ⅰ), who had been taking cyclosporine (CsA) as immunosuppressive agent were studied. The patients were randomly divided into group A and group B. CsA was replaced with FK506 (1∶75) in group A that included 50 patients. Group B including the other 43 patients served as control group. All patients were followed up at least three years. Renal functions, losses of creatinine clearance rates within 3 years, incidence of acute renal graft rejection and plasma TGF-?_ 1 concentrations were compared between the two groups.Results Three years later, there were 31 patients ( 62.0 % ) with stabilized or improved graft function in group A, and 4 patients ( 9.3 % ) in group B. The difference was significant (P