Prevention of cyclosporin A induced chronic nephrotoxicity in rats with cationic liposome-mediated antisense TGF-β1 oligodeoxynucleotides

摘要

To evaluate the effect of inhibition of transforming growth factor-beta 1 (TGF-β1) expression by liposome-mediated antisense oligonucleotides on chronic nephrotoxicity induced by cyclosporin A in rats.Methods Rats were on low salt diet and CsA was administered once every day by intraperitoneal injection (15 mg/kg every day) for 4 weeks.Antisense oligodeoxynucleotides for TGF-β1 were introduced into the nephritic kidney by liposome-mediated gene transfer method to inhibit the overproduction of TGF-β1.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-β1 mRNA was decreased by RT-PCR (P<0.01).By immunohistochemistry,the expression of TGF-β1 protein was inhibited significantly (P<0.01) in the liposome-mediated AODN rats with a comparable effect in preventing CsA chronic nephrotoxicity.Conclusion By inhibiting the expression of TGF-β1,liposome-mediated antisense oligonucleotides can attenuate the structural and function changes of kidney in CsA-induced chronic nephrotoxicity.10 refs,2 figs,1 tab.