Study On The Mechanism Of 1,25-dihydroxyvitamin D₃ Via STAT₃ Pathway In Renal Interstitial Fibrosis In UUO Rats

Objective:To investigate the effects of 1,25-dihydroxy vitamin D₃[1,25?OH?₂ D₃]in rats with unilateral ureteral obstruction?UUO?and its possible mechanism.Methods:54 healthy male Wistar rats weighing?200±10?g were used.They were randomly divided into sham group?group A?,UUO group?group B?and UUO+1,25?OH?₂D₃ group?group C?,and there are 18 rats in each group.The left ureter was ligated in group B and group C,but was free in group A without ligation.Group A was given 1,25?OH?₂D₃3ng/100g/d,and the other two groups were given the same amount of peanut oil.Six rats were randomly sacrificed 1 day,3 days and 7 days after surgery.Blood samples and left kidney tissue were obtained.The changes of serum creatinine,serum calcium and serum phosphorus levels in each group were detected.Pathological changes of kidney were observed by HE and Masson staining.The level of?-SMA and IL-17 in kidneys of each rat was detected by immunohistochemistry.The level of p-STAT₃ in rat renal tissue was detected by Western blotting.Results:?1?The changes of serum creatinine in each group:Compared with group A?Sham Group?,the serum creatinine level was significantly higher in group B?UUO group??P<0.05?;the serum creatinine level in group C?Medication group?was significantly lower than that in group B?UUO group??P<0.05?.?2?The level of blood calcium and phosphorus changes in each groups:The changes were slightly,and the differences was not statistically significant?P>0.05?.?3?The changes about the level of?-SMA protein expression in the rat kidney:The level of?-SMA in group B?UUO group?was significantly higher than that in group A?Sham Group?,and the difference was statistically significant?P<0.05?.Compared with group B?UUO group?,the level of?-SMA decreased significantly in group C?Medication group??P<0.05?.?4?The changes about the level of IL-17 protein expression in the rat kidney:The level of IL-17 in group B?UUO group?was significantly higher than that in group A?Sham Group?,and the difference was statistically significant?P<0.05?.Compared with group B?UUO group?,the level of IL-17 decreased significantly in group C?Medication group??P<0.05?.?5?The changes of p-STAT₃ in kidney of each group:The levels of p-SATA₃ in group B?UUO group?were significantly higher than those in group A?Sham Group?,and the difference was statistically significant?P<0.05?.Compared with group B?UUO group?,the level of p-STAT₃ was significantly lower in group C?Medication group??P<0.05?.Conclusion:?1?Renal fibrosis may be accompanied by increased expression of IL-17,and1,25?OH?₂D₃ may delay progression of renal fibrosis by down-regulating IL-17.?2?Renal interstitial fibrosis may be accompanied by increased expression of p-STAT₃.1,25?OH?₂D₃ may affect IL-17 by down-regulating the level of p-STAT₃ and ultimately affect the progression of renal interstitial fibrosis.