| [ Background and Objective ] Renal tubulointerstitial fibrosis (TIF) is involved in all of progressive renal diseases regardless of the initiating insult. TIF is often recognized as an endpoint outcome of chronic renal diseases, correlated better with deterioration of renal function and play a key role in the progression of chronic renal diseases. Unilateral ureteral obstruction (UUO) has emerged as an important model for the study of the mechanisms underlying renal fibrogenesis and also for the evaluation of the impact of potential therapeutic approaches to ameliorate renal disease because that the major characteristic of the UUO renal is TIF. Transforming growth factor- β1 (TGF-β1) and angiotensin II (AngII) are considered as two key factors in the progression of TIF and become the two targets in the treatment of TIF. Monopril and Losartan have been widely used in clinically for the treatment of chronic renal disease for their mechanisms of downregulation of local TGF-β1 , decrease in inflammatory cell infiltration and in proliferation of tubulointerstitial cells by inhibition of Angll actions through different pathway. Hepatocyte growth factor(HGF) has been more and more noticed as a renal protector for its untifibrosis fact in recently.Studies show that HGF can be downregulated by TGF-β1 and Angll. So it is reasonable for us to propose the following hypothesis : Monopril and Losartan might upregulate the expression of endogenous HGF by inhibition of Angll, and decrease the expression of TGF-β1, thereby stave the progression of TIF. In thisexperiment, we investigate the effect of Monopril and Losartan on the expression of HGF in the renal of rat after unilateral ureteral obstruction, to find out the protective mechanism of angiotensin - converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers(ARB).[methods] Female Sprague-Dawley rats were randomly assigned to five groups: sham-operated group(C group,n=6),operation group(UUO group,n=6), Monopril(10mg kg-1 d-1) treatment group after UUO(UUO+ACEI group,n=6), Losartan( 50mg kg-1 d-1 ) treatment group after UUO(UUO+ARB group,n=6) and combined treatment with the same dose of Monopril and Losartan group after UUO(UUO+ combined treatment group,n=6). Obstructed kidneys were harvested 14 days after operation. Systolic β100d pressure was measured using the tail-cuff method .The samples of β100d and the urine of 24 hours were collected to detect the concentration of serum creatinine, the quantity of urinary protein and creatinine .HE and Masson staining were performed ,as well as HGF, TGF-β1 and PCNA were immunostained by SP Kit in the obstructed kidney of all rats.[Results] By 14 days after operational) there were no significant difference in the β100d pressure of rats between all of groups (109.233+3.322 vs. 109.300 + 1.685 vs. 109.717+2.245 vs. 110.155 + 2.036 vs. 108.833 + 1.415, P =0.835) .neither in the quantity of urinary protein of 24 hours (0.230 +0.030 vs. 0.223 +0.029 vs. 0.222 + 0.025 vs. 0.257 +0.051 vs. 0.228 +0.043, P =0.473) ,and neither in the clearance of creatinine rate (0.332+0.029vs. 0.330+0.035 vs. 0.336+0.019 vs. 0.310+0.017 vs. 0.335 +0.031, P =0.466); (2) The range of expansion interstitium in UUO group increased significantly compared with what in shame operation group (2.100 +0.094 vs. 0.508 +0.176, P<0.001), as well as what in Monopril treatment group after UUO(2.100+0.094 vs. 1.875 + 0.178, P=0.049), so as what in Losartan treatment group after UUO (2.100+0.094 vs. 1.825+0.279, P=0.018), and in combined treatment group (2.100 +0.094 vs. 1.071 +0.165, P<0.001); The expansion of renal interstitium in combined treatment group decreased significantly compared with what in Monopril treatment group (1.071 +0.165 vs. 1.875 +0.178, P<0.001), and in Losartantreatment group (1.071+0.165 vs. 1.825+0.279, P<0.001); There were no significant difference in the expansion of renal interstitium of rats between Monopril treatment group and Losartan treatment group (1.875 + 0.178 vs. 1.825 + 0.279, P=0.6...
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