Sodium thiosulfate attenuates high phosphorous induced vascular calcification in rats with 5/6 nephrectomy / 中华肾脏病杂志

ABSTRACT

Objective To observe the expression of Klotho and Na+/Pi cotransporter in high phosphorous-induced rats with 5/6 nephrectomy and its relationship with vascular calcification,as well as to investigate the effect of early intervention by sodium thiosulfate (STS) on the progression of vascular calcification.Methods Either 5/6 nephrectomy (n=21) or sham operation (n=14) was conducted on 35 Sprague Dawley rats,who were then fed with high phosphorus (HP) diet or normal phosphorus (NP) diet for 16 weeks respectively.The rats were divided into 5 groups as follows(1) remnant kidney rats receiving HP diet (NHP,n=7),(2) remnant kidney rats receiving NP diet (NNP,n=7),(3) sham operation rats receiving NP diet (SNP,n=7),(4) sham operation rats receiving HP diet (SHP,n=7),(5) remnant kidney rats receiving HP diet with STS (THP,n=7).The treatment group was given STS intraperitoneally three times a week for 16 weeks.At the end of the 16th week,rats tail artery blood pressures were tested,serum creatinine (Scr),calcium (Ca2+),phosphorus (P3+),FGF23,iPTH and urine protein were examined.Throacic aorta and kidney were then removed.Vascular calcification was confirmed by Von kossa staining.Klotho and Pit-1 expression in aortas were determined by immunohistochemistry.Renal lesion was determined by PASM-Masson staining.Renal Klotho and NaPi-2a mRNA were determined by real time RT-PCR.Results After 16 weeks,Scr,p3+,FGF23,iPTH,uric protein and blood pressure were significantly higher in NHP than those in SNP rats (all P ＜ 0.05).PASM-Masson staining revealed typical renal pathology of chronic renal failure in NHP group.With the treatment of STS,THP rats showed significant decrease in Scr,t3+,FGF23,iPTH,uric protein and blood pressure by comparison with NHP group (all P ＜ 0.05).Significant vascular calcification was found in NHP group while NNP and SHP group occasionally had vascular calcification;THP group had marked alleviation of vascular calcification.The aorta and renal expression of Klotho decreased remarkably while expression of Pit-1 and NaPi-2a increased significantly in NHP compared with SNP group (all P ＜ 0.05).Accordingly,the aorta and renal expression of Klotho increased and Pit-1 and NaPi-2a decreased significantly in THP compared with NHP group (P ＜ 0.05).Conclusions The early intervention of sodium thiosulfate might regulate Klotho and Na +/Pi cotransporter expression in both aorth and kidney,decreasing serum phosphate,delaying progression of vascular calcification and improving renal function.