| Objective: Interstitial fibrosis and subsequent tubular atrophy are pivotal pathological changes that lead to end-stage kidney diseases. And tubulointerstitial injury plays more important role than glomerular damage on renal interstitial fibrosis. YSH may prevent mast cells from releasing inflammatory mediators such as Tryptase by degranulation. Therefore this study is to explore whether YSH exerted a role to block MCs in vivo and provide a new method and academic foundation for blocking TIF.Methods:(1)This study adopted the unilateral ureteral obstruction (UUO) animal model. Renal specimens from 75 male, weight 150±20g, Sprague-Dauley(SD) rats with UUO group, UUO+high-YSH treatment group, UUO+low-YSH treatment group, UUO+ACEI treatment group and Sham group was as controls, and each group wad 15 rats. Unilateral ureteral obstruction were used by ligating the left uretera, the sham group take the same operation but not ligated. YSH was administered daily at a dose 2.1ml/d,1.05ml/d in high and low-YSH treatment groups, day before UUO and daily for 6 weeks.(2)The dynamic histological changes of renal interstitial tissues were observed by HE staining.(3)TB staining and Tryptase immunostained by PV kit in the obstructed kidney of all rats were performed to observe the morphological and the regularity of distribution of MCs. (4)Shape and ultrastructure features of MCs were observed using electron microscopy.(5) TGF-β1 andα-SMA were immunostained by PV kit in the obstructed kidney of all rats.(6)The concertration of SCR, BUN, UCR, UUN and the quantity of 24-hour urinary protein were also detected.(7)All of the enumeration data was recorded asχ±s. After tested by the test for homogeneity of variance, the data was analyzed by one-way analysis of variance. The relationship between two groups was tested by linear correlation. The standard of significant difference was defined as P=0.05. The SPSS 12.0 software packet was applied to the statistic analysis.Results: (1) 6 weeks after UUO, the tumafaction and atrophy in renal parenchyma of obstructed kidneys were measured obviously. Fibrous material and monocyte infiltration increased in the interstitial space. Furthermore, thickening of interstitial space of the tubular basement memberance and widening of the interstitial space of the renal cortex were noted. Hypertrophy or atrophy of juxtaglomerular tubules were also noted. There were cellular or albumin casts in partly tubules. But the glomerular damage can't be seen significantly in all groups. (2) The numbers of MCs in other groups were highter significantly than that in sham group (P<0.01). The number of MCs and the expression of Tryptase in treatment groups decreased markedly (P<0.05 or P<0.01) compared with UUO group. (3) The expression of the other two kind of proteinum in treatment groups decreased markedly (P<0.05 or P<0.01) compared with UUO group. The tubulointerstitial damage index and the expression of TGF-β1 andα-SMA were significant increased compared with Sham(P< 0.01) in UUO, but those indicates decreased in treatment-groups. There was no significant difference between YSH-high dosage group and ACEI group (P>0.05) . (4) And the differences of 24-hour urine protein volume and SCR have no statistically significant(P>0.05). The concertration of BUN, UCR, UUN in treatment groups decreased markedly (P<0.05 or P<0.01) compared with UUO group. MCs were positively correlated with interstitial lesions (r=0.78, P < 0.01) and Tryptase were also positively correlated with TGF-β1 (r=0.887, P=0.017<0.05).Conclusion:1. YSH can alleviate the pathological changes of renal interstitial fibrosis in UUO rats. Its effects were similar to benazepril;2. Renal interstitial infiltration of mast cell was tightly associated with the severity of renal interstitial fibrosis.YSH can evidently inhibie UUO-induced renal interstitial fibrosis in rats, which might be related with its action of suppressing the degranulation of MCs;3. YSH inhibited the increase of TGF-β1, Tryptase andα-SMA after UUO, its action may be by the way of MC—TGF-β1—Smad.
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