RESUMEN
Objectives To observe the expressions ofα-smooth muscle actin (a-SMA) and type III collagen (Col-III) of tubuloin-terstitial ifbrosis(TIF) induced by unilateral ureteral obstruction (UUO) in rat and the intervention effect of supplemental hydrogen sul-ifde (H2S). Methods Ninety-six male Sprague-Dawley rats were randomly divided into 4 groups, sham-operated group, UUO model group, NaHS low-dose group and high-dose group. TIF rat model was established via UUO. After UUO operation, low-dose and high-dose group were intraperitoneally injected twice a day with 1.4μmol/kg and 7.0μmol/kg NaHS, respectively. Sham-operated group and UUO model group were given an equivalent volume of normal saline. Eight rats in each group were killed randomly at 7, 14 and 21 days after UUO operation. The concentration of plasma H2S was detected using deproteinization. Renal tubulointerstitial damage was evaluated with routine Hematoxylin and Eosin staining and Masson staining under microscope. The expressions ofα-SMA, Col-III were measured with immunohistochemistry. Results Compared with sham-operated group, renal tubulointerstitial injury was severer in UUO model group and was alleviated after intervention of NaHS. There was signiifcant difference in tubulointerstitial injury among all groups (P0.05). Conclusions TIF induced by UUO is associated with decreased level of endogenous H2S. H2S supplementation can ameliorate the development of UUO-associated TIF in part through down-regulating the expressions ofα-SMA and Col-III in renal tissues. However, a dose dependent manner between the two doses of exogenous H2S supplementation was not observed.
RESUMEN
Objective To investigate the effects of hydrogen sulfide (H2S) on the tubular interstitial fibrosis and on the levels of kidney injury molecule-1 (KIM-1) and ectodermal dysplasia-1 (ED-1) in the process of renal interstitial fibrosis in rats with unilateral ureteral occlusion(UUO).Methods Ninety-six Sprague-Dauley (SD) male rats were divided into 4 groups randomly:sham-operated group (n =24),model group (n =24),low-dose therapy group (n =24) and high-dose therapy group(n =24).The rats in the model group and treatment groups were ligated at the left ureter and UUO was induced,meanwhile,the rats in the control group were free from the left ureter ligation.Rats received sodium hydrosulfide(NaHS) in traperitoneatly(1.4 μmol/kg,twice a day),and NaHS(7.0 μmol/kg,twice a day),respectively.Rats in sham-operated group and the model group were injected intraperitoneally with identical voluminal 9 g/L saline.Eight rats in each group were sacrificed randomly at the 7 days,14 days and 21 days,respectively.The concentration of plasma H2S was detected.Renal tubular interstitial damage and interstitial fibrosis were evaluated with routine HE staining and Masson staining under microscope,and both of them were used to evaluate the obstruction of renal histopathological changes.The expressions of ED-1 and KIM-1 were measured with immunohistochemical staining.Results 1.The pathological findings showed that the renal tubular interstitial changes were not obvious in the shamoperated group.The tubular epithelial cells in the model group and treatment groups showed swelling and vacuoles degeneration,with renal interstitial broadening,interstitial cells and extracellular matrix increasing.The renal tubular interstitial pathological injury of model group and treatment group were more serious than those in the sham-operated group at each time point(P ＜ 0.05).The renal tubular interstitial pathological injury of the treatment groups were obviously lower than that in the model group(P ＜0.05).However,there was no statistically significant difference between highdose therapy group and low-dose therapy group(P ＞ 0.05).2.Immunohistochemical analysis showed that expressions of ED-1 and KIM-1 in renal tubular interstitices in the model group and the treatment groups were higher than those in the sham-operated group at each time point(P ＜ 0.05).The expressions of ED-1 and KIM-1 in renal tubular interstitices in the treatment groups were obviously lower than those in the model group(P ＜ 0.05).There was no statistically significant difference between the high-dose therapy group and the low-dose therapy group(P ＞0.05).3.Plasma H2S levels in model group and treatment group were lower than those in the sham-operated group at each time point (P ＜ 0.05).The plasma H2S level of the treatment group was obviously higher than that in the model group(P ＜ 0.05).However,there was no statistically significant difference between high-dose therapy group and low-dose therapy group (P ＞0.05).Conclusions H2S implements renal protection effect partly by reducing the expression of ED-1 and KIM-1 in tubule interstitices to ease tubular interstitial fibrosis.