Effect of Active Vitamin D3 on Rat Renal Tubulointerstitial Fibrosis and Its Possible Mechanism
- VernacularTitle:活性维生素 D3对大鼠肾小管间质纤维化的影响及其机制研究
- Author:
Ruiri JIN
1
;
Xiaorong BAO
Author Information
1. 复旦大学附属金山医院肾内科
- Keywords:
Active vitamin D3;
Renal tubulointerstitial fibrosis;
Tubular epithelial-myofibroblast transdifferentiation;
Transforming grow factor β
- From:
Chinese Journal of Clinical Medicine
2015;(6):722-726
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To observe the effect of active vitamin D3 on renal tubulointerstitial fibrosis and its possible mechanism . Methods : Forty male SD rats were randomly divided into four groups :sham operation group(Sham group ,n= 10) ,unilateral ureteral obstruction (UUO) model group (UUO group ,n= 10) ,UUO model treated with low dose of active vitamin D3 group (LV group ,n= 10) ,and UUO model treated with high dose of active vitamin D3 group (HV group ,n= 10) .UUO model was estabished by ligating the left ureter .The left ureter was only dissociated without ligation in Sham group .LV group and HV group were given active vitamin D3 (dissolved in peanut oil) at a dose of 0 .03 μg/(kg ? d) and 0 .06 μg/(kg ? d) ,respectively , by intraperitoneal injection .Sham group and UUO group were given the same volume of peanut oil by intraperitoneal injection . Rats were killed 14 days after surgery .Blood and kidney samples were collected .And serum calcium ,phosphorus ,creatinine (SCr) ,and parathyroid hormone (PT H ) were detected . The kidney pathological changes involving renal tubulointerstitial injury and fibrosis ,were observed after H-E and Masson staining with optical microscope .The expressions of α-smooth muscle actin (α-SMA ) 、E-cadherin , and transforming grow factor β (TGF-β) in renal tubulointerstitial tissues were detected by immunohistochemistry .Results :Compared with those in UUO group ,the SCr level ([39 .0 ± 1 .83] μmol/L ,[36 .0 ± 2 .11]μmol/L vs .[43 .1 ± 5 .55] μmol/L) ,tubulointerstitial fibrosis index (2 .00 ± 0 .12 ,1 .70 ± 0 .10 vs .2 .80 ± 0 .11) ,expression of α-SMA (0 .22 ± 0 .02 ,0 .20 ± 0 .03 vs .0 .24 ± 0 .02) ,and expression of TGF-β (0 .26 ± 0 .03 ,0 .25 ± 0 .03 vs .0 .32 ± 0 .04) in LV group and HV group decreased significantly (P< 0 .05) ,while the expression of E-cadherin (0 .30 ± 0 .08 ,0 .34 ± 0 .11 vs .0 .22 ± 0 .07 ) increased . Compared with those in LV group , the SCr level , tubulointerstitial fibrosis index , tubulointerstitial injury index ,expression of α-SMA ,and expression of TGF-β ,in HV group decreased significantly ( P <0 .05) ,while the expression of E-cadherin increased (P< 0 .05) .Correlation analysis showed that the expressions of TGF-β andα-SMA were positively correlated with tubulointerstitial fibrosis index . E-cadherin was negatively correlated with tubulointerstitial fibrosis index .TGF-β was positively correlated with α-SMA .E-cadherin was negatively correlated with TGF-β .α-SMA was negatively correlated with E-cadherin .Conclusions : Active vitamin D3 can relieve renal tubulointerstitial fibrosis in UUO rats .Its possible mechanism is that the tubular epithelial-myofibroblast transdifferentiation (EM T ) is suppressed by inhibiting the over expression of TGF-β so as to relieve the renal tubulointerstitial fibrosis .The effect of the high dose of active vitamin D3 for relieving renal tubulointerstitial fibrosis is superior to that of low dose of active vitamin D3 .
