| Objective To observe the effect of 1,25-(OH)2D3(Calcitriol Soft Capsules) on glomerular and renal interstitial fibrosis in 5/6 rats and discussed the possible mechanism.Methods Ten healthy male SD rats(age 2 months old,weight about 200g) were randomly selected into normal control group(group N) from forty healthy male SD rats after 1 week adapting feeding,the other was divided into surgery group to establish 5 / 6 nephrectomy and resection of the renal failure model,2 weeks after operation,tested serum urea nitrogen(BUN), creatinine(CR). BUN of each group.Cr is significantly higher than normal group of rats,which means success of building model.According to creatinine values,rats were divided into 2 groups: CRF group(group C), CRF+1,25-(OH)2D3(Calcitriol Soft Capsules) treatment group(group D).In D group was given 50ng/100 ng Calcitriol Soft Capsules capsules which is dissolved in 1 ml peanut oil orallyby gavage, twice a week;the other two groups were given 1 ml peanut oil by gavage twice a week. After continuous intervention, each group was randomly killed half rats respectively in 4 and 8 weeks, collected specimens of blood, urine and renal tissue samples, testedserum Ca and P,serum urea nitrogen(BUN), creatinine(CR) and 24 h urinary protein quantitative, observe the degree of rats renal fibrosisby optical endoscope,pathological examination,HE staining and Masson staining,using image analysis system for semi quantitative analysis and TGF-?1 and HGF expression in rat renal tissue were detected by immunohistochemical method.Result 1)24 hours urinary protein quantitative change: compared with the group N, group C and group D 24 hours urinary protein quantitatively significantly increased, in which the C group was the highest, the comparison between these three groups were statistically difference(P < 0.05). 2)The changes of serum Ca and P: compared with N group, the serum Ca level of C group decreased, which is increased in group D, comparison between these three groups were statistically different(P <0.05); the serum level of P between N,C,D groups is no significant difference(P >0.05.). 3) The change of serum BUN, Cr: compared with the group N, serum levels of BUN, Cr was significantly increased in group C and group D,among these,group C was the highest, the comparison between these three groups were statistically difference(P < 0.01). 4)Under light microscope, there was no obvious pathological change in group N glomerular and renal interstitial while glomerular and tubulointerstitial fibrosis was significantin group C, group D glomerular and tubulointerstitial fibrosis degree is lower than group C. 5)Pathological section and hematoxylin and eosin staining: compared with the group N, glomerular and renal tubule matter damage pathology score was increased significantly in group C and group D, group C was highest among the three groups comparisonis statistically significant difference(P < 0.01). 6)Masson staining results: Compared with the group N, the relative area of positive collagen in group C and group Dwere significantly increased(P<0.01), while the relative area of positive collagen in group D was lower than in group C(P <0.05). 7)TGF-?1, HGF immunohistochemical results: Therewas little TGF-?1expression in group N renal tubular interstitialtissue,while TGF-?1 expression in group C and group D renal tubular interstitialtissue is significantly higher than in group N(P < 0.01), whereas in group D expression of TGF-?1 is lower than in group C(P < 0.05); There was little HGF expression in group N renal tissue, there almost be no expression of HGF in group C and group D glomerular tissue. Compared with group N, the expression of HGF in group C and group D renal tubular interstitial tissuewas significantly higher(P<0.01), and the expression of HGF in renal tubule interstitial tissue of group D was higher than that of group C(P <0.05).Conclusion 1.High dose of Calcitriol Soft Capsules impact therapy can reduce the level of urinary protein in chronic renal failure rats and delay the progression of chronic kidney disease. 2. High dose Rocaltrol impact therapy can inhibit glomerular and renal tubule interstitial fibrosis, mainly inhibit renal interstitial fibrosis, the mechanism of action may be related to inhibiting TGF-?1 expressionand the promotion of the HGF expression. |
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