| Objective:This experiment through setting up rat models of renal interstitial fibrosis(RIF)---unilateral ureteral obstruction(UUO) model, to dynamically observe the influence of YiShenHuaYu Recipe(YSHYR) on renal function of UUO rats, the pathological changes in renal tissue, and the content of hydroxyproline(Hyp) in renal tissue, the expression of platelet derived growth factor BB(PDGF-BB) and matrix metalloproteinase-1(MMP-1) mRNA,tissue inhibitor of metalloproteinase-1(TIMP-1) mRNA in the rats of RIF. To discuss some possible mechanisms of treating the rats with renal interstitial fibrosis.Methods:162 SD male rats were randomly divided into sham-operation group, model group, the valsartan treatment group,YSHYR high-dose, middle-dose and low-dose treatment group, each with 27 rats. Except the rats of sham group were only separated the left ureter but given no ligation, the other five groups were used single side ureteral ligation way to establish rat UUO model of RIF. The next day after operation beginning gavage. Sham-operation group and model group was administrated 0.9% 20mL/Kg saline gastric lavage, YSHYR high-dose, middle-dose and low-dose group was each given 32g/Kg·d, 16g/Kg·d, 8g/Kg·d, and the valsartan group to be Valsartan Capsules dissolved dilution 13.3mg/Kg·d. The drug volume of administration was 20 m L/Kg·d each group. The rats were respectively killed at the 7, 14 and 28 days after operation and collected the specimen for test. To text the changes of kidney function by drawing blood from abdominal aorta.To observe the renal pathological changes of UUO model rats and RIF score by light mirror adopting HE and Masson staining method. To detect the hydroxyproline content of renal tissue by alkaline water solution and to text the changes of expression on PDGF-BB of renal tissue by ELISA method. The expression of MMP-1mRNA and TIMP-1mRNA in renal tissue was detected by Real-time PCR.Results:1.The impact of YiShenHuaYu Recipe on serum BUN, Scr and CysC of rats for each groupSerum BUN, Scr and CysC of sham group rats had no obvious change at each time point; compared with the sham group,those of model group and treatment groups have different rise level in the same time point(P<0.05 or P<0.01), and with the extension of time gradually increased; compared to the model group, those of the treatment groups were reduced in different level at the same time point(P<0.05 or P<0.01), in which the YSHYR high-dose group and valsartan group decreased most significantly, and there has no statistical difference between this two groups(P>0.05).2.Effects of YiShenHuaYu Recipe on pathomorphological changes of rats renal tissue for each groupHE and Masson staining with light microscope showed that, there is no significant change in the organization structure of the kidney at each time point; the pathological changes happened in the model group is the most serious, which gradually increased with time, mainly for the expansion, atrophy and disappear of the renal tubules, inflammatory cells infiltration and fibrosis of renal interstitial. Compared to the model group, those of the treatment groups are lighter in different degree at the same time point, and YSHYR high-dose group and valsartan group are the lightest.3.Effect of YiShenHuaYu Recipe on the expression of Hyp in renal tissue of rats for each groupExpression of Hyp in the sham group has no obvious change at each time point; compared to the sham group, Hyp in model group and treatment groups have different rise level in the same time point(P<0.01), and with the time prolong gradually rise, especially for the model group.Compared to the model group, Hyp content of treatment groups decreased, among them, YSHYR high-dose group and the valsartan treatment group decreased obviously(P<0.01), and has no statistically significant difference between them(P>0.05).4.The impact of YiShenHuaYu Recipe on the expression of PDGF-BB in renal tissue of rats in each groupNo obvious change showed in the sham group at each time point.Compared to the sham group,PDGF-BB of model group and treatment groups have increased to some extent(P<0.01), and it increased with time. Compared with the model group, PDGF-BB in treatment groups reduced in different degrees, especially for the YSHYR high-dose treatment group and valsartan treatment group(P<0.01), and with no statistical difference between them(P>0.05).5.Influence of YiShenHuaYu Recipe on the expression of MMP-1mRNA, TIMP-1mRNA in renal tissue of rats for each groupCompared with the sham group, the expression of MMP-1mRNA and TIMP-1mRNA in model group and treatment group showed increased in different degrees, and the expression of them continued to increase with time; while at the same time the expression of TIMP-1mRNA increased more than that of MMP-1mRNA. Compared with the model group, each group had no significant difference in the expression of renal tissue of rats with MMP-1mRNA(P>0.05); and the expression of TIMP-1mRNA gradually decreased, among them, YSHYR high-dose group and the valsartan treatment group decreased obviously(P<0.05 or P<0.01), and with no statistical difference between them(P>0.05).Conclusion:1.YiShenHuaYu Recipe can reduce the content of serum BUN, Scr and CysC in UUO rats,improve the function of kidney and alleviate the pathological damage of kidney tissue, delay the development of RIF.2.YiShenHuaYu Recipe may reduce the content of Hyp and inhibit the expression of PDGF-BB in renal tissues, so as to reduce the degree of RIF.3.YiShenHuaYu Recipe may play a role of protecting kidney by influencing the expression of MMP-1mRNA, TIMP-1mRNA, adjusting the imbalance of MMP-1/TIMP-1 in mRNA level in obstructive kidney and promoting the degradation of ECM. |
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