| Objective:Chronic kidney disease(CKD)as the major disease endanger public health around the world, and it prevalences of vitamin D insufficient and lacking.A large number of experimental studies have confirmed that vitamin D can not only make calcium and phosphorus and bone metabolism balance through act on the kidney,bone,parathyroid and so on,but also have renal protective effect independent of calcium and phosphorus metabolism regulation.Clinical and experimental studies found that short-term1,25(OH)2D3can protect podocyte, reduce proteinuria and delay the progress of chronic renal failure, but it’s long-term mechanism remains unclearly.This study used5/6nephrectomy rat,and investigated long-term(24w)1,25(OH)2D3effected on proteinuria,renal function,the structure and function of podocyte.Methods:12S-D rats after5/6nephrectomy were prepared for chronic reanl failure model, and they were divided into model group(group D,n=6),1,25(OH)2D3group (group C,n=6),and we prepared sham operation group (group N,n=6) at the same time.group C rats were given1,25(OH)2D3(3ng/100g body wt/day) administered by intraperitoneal injection a total of24weeks three weeks after surgery.and testing serum creatinine(SCr),urine protein(UP),urine creatinine(UCr) at week3,12,24after surgery. At week24, the rats were sacrificed, and renal tissue for routine pathology and electron microscopy,examined renal organizational structure and podocyte ulterstructure changes.immunohistochemical was employed to detected the expression of glomerulus vitamin D receptor (VDR), podocalyxin, beta-catenin and snail,and analysis of the relationship with proteinuria and renal function.Results:(1) At week3to week24, the SCr and UP of group C and D were higher than group N (all p<0.05), but at week24, SCr and UP of group C lower than group D (all p<0.05). at week3to week24,Ccr of group C and Dwas were lower than group N (p<0.05), and there was no differences between the first two groups (p>0.05). at week3to week24,the serum calcium and phosphorus levels showed no significant difference between the three groups(all p>0.05).(2) pathology tests showed that glomerular sclerosis significantly increased in the group D and C compared with group N (p<0.05),but group C lighter than group D (p<0.05). electron microscopy showed that podocyte ultrastructure apparently damaged in the group D and C compared with group N,and group C lighter than group D.Immunohistochemical proved that podocalyxin and VDR mainly expressed in podocytes, and beta-catenin, snail do not obviously expressed in glomerular of group N rats,but the expression of podocalxin and VDR obviously reduced,and beta-catenin, snail increasely expressed in group D and C(all P<0.05),located mainly in the podocytes.The expression of glomerular podocyte VDR and podocalyxin of group C obviously up-regulated(all p<0.05), beta-catenin and snail expression obviously down-regulated (all p<0.05) in contrast with group D.The correlation analysis showed that expression of VDR was negatively correlated with proteinuria and SCr,and the expression of beta-catenin was positive correlatied with proteinuria and SCr.Conclusion:1.lone-term Vitamin D can reduce the level of UP and SCr,and reduce the degree of glomerulosclerosis of uremic rats.2.Inhibitory effection of lone-term Vitamin D supplementation on uremic-induced vitamin d receptor and podocalyxin expression decrease.3. Inhibitory effection of lone-term Vitamin D supplementation on uremic-induced wnt/beta-catenin-snail signal pathway activation in podocytes.So it may be the important mechanism of vitamin D protect podocytes, reduce proteinuria and slow the progression of chronic kidney disease. |
PDF Full Text Request