ABSTRACT
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.
ABSTRACT
Objective:To determine the role and mechanism of tranilast preventing the progression of tubulointerstilial ifbrosis in diabetic kidney disease (DKD). Methods:Sprague-Dawley rats were randomly divided into a control group (n=6), DKD model group (n=8), low dose tranilast group [200 mg/(kg.d), n=8], and high dose tranilast group [400 mg/(kg.d), n=8]. Tranilast was administered daily after the model was built. Rats were sacrificed at day 56, 24 hour urine was collected to measure 24-hour urine albumin excretion, and blood was collected to determine the renal function and serum albumin. Then the kidneys were harvested and subjected to studies. The expression of C3aR, E-cadherin,α-SMA, fibronectin(FN), collagen I (Col I), stem cell factor (SCF) and c-kit were detected by immunohistochemical staining respectively. The expression of E-cadherin,α-SMA, FN, Col I, SCF and c-kit protein was analyzed by Western blot, and the expression of FN, Col I, SCF and c-kit mRNA was examined by RT-PCR. Results:Tranilast can inhibit the inifltration of mast cells in the kidneys of DKD rats. The expression ofα-SMA in the kidneys of DKD rats inereased signiifcantly (P Conclusion:Mast cells participate in and aggravate the renal tubulointerstitial fibrosis in DKD rats. Tranilast can reverse the EMT of renal tubular cells and inhibit the tubulointersitial fibrosis of DKD by blocking the inifltration of mast cells induced by SCF/c-kit pathway.