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, P3+, 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. 相似文献
Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1(ApoB/ApoA-1) ratio on the incidence of ischemic stroke(IS) or coronary heart disease(CHD) in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein(CRP) level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios(HRs) and 95% confidence intervals(CIs) for the IS and CHD events in all the subgroups.Results The HRs(95% CI) for IS and CHD were 1.33(0.84-2.12),1.14(0.69-1.88),and 1.91(1.17-3.11) in the ‘low CRP level with high ApoB/ApoA-1',‘high CRP level with low ApoB/ApoA-1',and ‘high CRP level with high ApoB/ApoA-1' subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1' subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1' subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population. 相似文献