Effect Of Cordyceps Polysaccharide On The Tubular Epithelial Mesenchymal Transition In Unilateral Ureteral Obstructive Mice

AIM: Renal interstitial fibrosis is the common pathway of progressive renal disease to the end stage renal failure. A large number of studies demonstrated that the degree of tubulointerstitial fibrosis (TIF) was correlated with prognosis of renal disease. Recently, it was found that tubular interstitial cell was not only a sufferer but a participant of fibrosis progression. More and more basic experiments indicated epithelial-mesenchymal transition was a key event of TIF. Inhibition or reversion of EMT might be a potential treatment for TIF. As the main compound of traditional herb Cordyceps, Cordyceps polysaccharide could regulate immune function, reduce blood glucose and inhibit progression of chronic renal disease. Results of long-term clinical practices proved cordyceps polysaccharide played an important role in protecting the renal function of patients with CRD. But the mechanism has not been known well. Recent studies indicated that cordyceps could suppress the tissue fibrosis such as hepatic fibrosis, which might be involved in its renal protection . In this study, we investigated the effect of cordyceps polysaccharide on the tubular epithelial mesenchyal transition in mice with unilateral ureteral obstruction (UUO).METHODS: Renal interstitial fibrosis was induced by UUO in CD-1 male mice. CD-1 mice were randomly devided into 3 groups: 1) Control group (N=8): the ureters of mice were exposed, but not ligated. 2) UUO group (N=10): mice were performed UUO operation in an established procedure. 3) UCp group (N=10): mice were treated with cordyceps polysaccharide (160mg/kg) after UUO operation. Mice were sacrificed at day 7 after surgical operation. The kidneys removed were fixed in 10 % phosphate buffered formalin. Kidney sections from paraffin embedded tissues were prepared at 4μm thickness using a routine procedure. Histological and immunohistochemical methods were used to analyze pathological changes andα-SMA,E-cadherin,ILK,CTGF expression in renal tissue. Real time PCR was used to observe the expression ofα-SMA,E-cadherin,ILK,CTGF mRNA in renal tissue. Western blot was used to quantitatively analyze the protein expression of ILK and CTGF in the obstructive kidney.Results: The mice in UUO group suffered from renal interstitial fibrosis were identified by histological analysis. Cp treatment obviously reduced tubular lesions and attenuated intestitial fibrosis(11.25±1.07% vs.19.39±1.52%, P<0.01). The results from immunohistochemistry indicated that there were increasing expression ofα-SMA and losing expression of E-cadherin in UUO kidney compared with control one(P<0.01). Cp could attenuate the loss of E-cadherin expression compared with UUO one (P<0.01). With Cp treatment, the expressions ofα-SMA protein were alleviated significantly (P<0.01). And the results of real time PCR indicated the expression ofα-SMA mRNA was increased and E-cadherin was decreased in UUO kidney compared with control one (P<0.01). Interestingly, there were significiantly increased expression of CTGF and ILK protein and mRNA in UUO kidney compared to control one (P<0.01). After Cp treatment, the expression of CTGF and ILK protein was decreased compared with UUO one (P<0.01). And compared with UUO group, the expression of CTGF and ILK mRNA was inhibited in Cp one (P<0.01).Conclusion:...