Effect Of Combination Therapy Of Glycyrrhizin Acid And Prostaglandin E1on Renal Interstitial Fibrosis In Rats

Background:Renal interstitial fibrosis is a common consequence of chronic kidney diseases that leads to chronic renal failure. Several pathways are involved in renal interstitial fibrosis, such as inflammation, oxide stress and imbalance of relocated cytokines. Some studies have shown that,cytokines such as transforming growth factor-β1(TGF-β1) and connective tissue growth factor(CTGF) play key roles in the development of renal interstitial fibrosis of human and animals. Most of those cytokines were produced by the renal interstitial cells, so antagonistic adverse effects of cytokines has become an important part.Objective:To investigate the mechanism of renal interstitial fibrosis after unilateral ureteral obstruction(UUO)and the effect of glycyrrhizin acid(GA) and prostaglandin E1(PGE1) on expressions of TGF-β1and CTGF in rats, and to provide experimental evidence for studies on renal interstitial fibrosis.Methods:Rat models of unilateral ureteral obstruction (UUO) were established by ligating left ureteral.120rats were randomly divided into5groups:sham group,model group, GA group,PGE1group and GA+PGE1group.8rats in each group were sacrificed at days7,14and21after operation.The serum level of creatinine(CREA) was determined, and the histopathological examination of renal tissue were observed by HE staining under optical microscope. The serum levels of transforming growth factorβ1(TGF-β1) and connective tissue growth factor(CTGF) were detected by ELISA. The expressions of CTGF and TGF-β1in renal tissue were observed by immunohistochemical staining.Results:1)At day14after operation, the serum level of TGF-β1in model group was 104.41±3.29ng/mL, and the level of the sham group was32.86±0.14ng/mL;At day21after operation, the serum level of TGF-β1in model group was142.25±8.01ng/mL, and the sham group was32.94±0.53ng/mL.(All the results have statistically difference, P<0.05).2)At day14after operation, the serum level of CTGF in model group was183.93±4.69pg/mL, and the level of the sham group was105.31±0.31pg/mL;At day21after operation, the serum level of CTGF in model group was366.41±3.68pg/mL, and the sham group was104.98±0.21pg/mL.(All the results have statistically difference, P<0.05).3)At day14after operation, the expressions of TGF-β1in model group was (16.48±0.47)%, and the level of the sham group was(3.07±0.08)%;At day21after operation, the expressions of TGF-β1in model group was(34.89±0.58)%, and the sham group was(3.07±0.09)%.(All the results have statistically difference, P<0.05).4)At day14after operation, the expressions of CTGF in model group was7.01±0.44%, and the level of the sham group was(0.99±0.15)%;At day21after operation, the expressions of CTGF in model group was(14.74±0.74)%, and the sham group was(0.98±0.23)%.(All the results have statistically difference, P<0.05).5)In GA+PGE1group the degree of renal interstitial damage,and serum contents and expressions of TGF-β1and CTGF were remarkably reduced compared with those in other treatment groups(P<0.01).Conclusion:GA and PGE1have potent preventive effect on RIF in UUO rats,which may be related to down-regulation of TGF-β1and CTGF.