| Background and Objective: Renal interstitial fibrosis, RIF is often recognized as an endpoint outcome of chronic renal disease, and plays a key role in the progression of chronic renal diseases. Many scholar want to find out the effective medicine to inhibite or ameliorate the renal interstitial fibrosis. Vitamin D endocrine system plays an essential role in calcium homeostasis and bone metabolism and research during the recent years has revealed a diverse range of biological actions of cell growth, immunomodulation and control of other hormonal systems. Some foreign literature has showed that vitamin D can inhibite the progression of the renal interstitial fibrosis in human and animals. A lot of cytokine have contributed to the progression of renal interstitial fibrosis, and hepatocyte growth factor, HGF has been more and more noticed as a renal protector for its untifibrosis fact recently. Unilateral ureteral obstruction, UUO has emerged as an important model for the study of the mechanisms of renal fibrosis and also for the evaluation of the impact of potential therapeutic approaches to ameliorate renal disease. In this experiment, we detected the expression of HGF, transforming growth factor-β1, TGF-β1 andα-smooth muscle acting,α-SMA on rat renal interstitial interstitium after UUO and to study the inhibiting effect of 1, 25(OH)2D3 on renal interstitial fibrosis.Methods: Forty male Sprague-Dawley rats were randomly assigned to five groups, each group had 8 animals:①UUO+1,25(OH)2D3 treatment group: Unilateral ureteric obstruction(UUO) + 1,25(OH)2D3 3ng/100g body wet /day by intraperitoneally (I.P) daily, and had administrated for 56 days.②UUO operation group: only operated the unilateral ureteric obstruction.③UUO+Benazopril group: benazopril hydrochloride tablets 0.17mg/100g body wet/day by intragastric administration daily, and had administrated for 56 days.④sham operated +1,25(OH)2D3 group: 1,25(OH)2D3 3ng/100g body wet /day by I.P daily, and had administrated for 56 days.⑤sham operated group. Obstructed kidney was harvested nine weeks after operation. The sample blood were collected to detect the concentration of serum calcium, blood urea nitrogen(BUN) and serum creatinine (Scr). HE staining were of performed, as well as HGF, TGF-β1 andα-SMA were immunohistochemistry by Two-Step Histostaining Reagent in the obstructed kidney of all rats. HGF and TGF-β1 mRNA expression were determined by RT-PCR.Results:1 HE staining displayedThe structure of glomcrulus and tubules in sham operation group was normal. In control UUO operation group the structure of tubule was innormal, some tubular cells had atrophied and deformed. In the UUO+1,25(OH)2D3 treatment group the degree of the transmutation was less than the UUO operation group. There was no significant difference between UUO+1,25(OH)2D3 treatment group and UUO+Benazopril group.2 The immunohistochemistry staining displayedThe expression of HGF in tubulointerstitium of UUO group was significantly higher than what in shame operated group (P<0.01), also was higher than what in UUO operation group(P<0.001). There was no difference between UUO+ 1,25(OH)2D3 treatment group and UUO+Benazopril group(P<0.01). The expression of TGF-β1 in tubulointerstitium of UUO+1,25(OH)2D3 treatment group was lower than what in control group(P<0.001). There were no significant difference in the expression of TGF-β1 protein between UUO+1,25(OH)2D3 treatment group and UUO+Benazopril group(P>0.05).3 The results of RT-PCRThe expression of HGF in UUO+1,25(OH)2D3 treatment group increased what compared with sham operated group(P<0.05). The expression of TGF-β1 increased what compared with sham operated groups (P<0.01). The expression of TGF-β1 was inhibited in UUO+1,25(OH)2D3 treatment groups. There were no significant difference in the expression of TGF-β1 mRNA between UUO+1,25(OH)2D3 treatment group and UUO+Benazopril group(P>0.05). 4 The level of serum calcium, BUN, Scr in the animalThere was no statistical significance among the level of serum calcium in the five groups(P>0.05). In comparison with shame operated group, the level of BUN and Scr in UUO operation group had increased (P<0.05). In comparison with UUO operation group, the level of BUN and Scr in UUO+1,25(OH)2D3 treatment group and UUO+Benazopril group had significant decreased(P<0.05).Conclusions:1 The fibrotic change of kidney was not significant when 1,25(OH)2D3 effected on the animal. The structure of the renal glomcrulus and tubules and the renal function of the animal were normal.2 1,25(OH)2D3 can stare the progression of renal tubulointerstitial fibrosis through the mechanism of upregulation of HGF, downregulation of TGF-β1 directly or indirectly.3 1,25(OH)2D3 can abrogate the myofibroblastic activated, and block tubular epithelial to mesenchymal traisition.4 The dose of 1,25(OH)2D3 in this experiment was safe to the animal, and there was not significantly side effect on the animal. It showed that it safe to use adequated dose of vitamin D to inhibite the renal interstitial fibrosis.
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