The Expression Of C5aR In Renal Tissue Of Rats Following Unilateral Ureteral Obstruction

Reserch backgroundThe reserch shows that the relation between renal interstitial disease and the progression of chronic kidney failure is closely.Renal interstitial fibrosis is a common feature of progressive renal diseases.It is a very hots pot to study the pathological process and mechanism of renal interstitial disease and search a new target for delaying and blocking the progressive of renal fibrosis.Although most reseachers try to block the progression of renal interstitial fibrosis,there isnot a satisfying result.The major pathological process of renal interstitial fibrosis includs the injuriing of kidney tubules and interstitial tissue,invading of inflammatory cell,the increasing of transforming growth factor-β1(TGF-β1),Connective Tissues growth factor)(CTGF),platelet-derived growth factor(PDGF)etal,and the decresing of hepatocyte growth factor(HGF),and decorin etal;the increment of myofibroblast;the accumulatio of extracellular matrix(ECM).The TGF-β1 was been known as the most important promoting fibrosis factor.Although most researchers tried to block the progression of Renal interstitial fibrosis by restrainning the TGF-β1,it needs a lot of works to make use of TGF-β1 for clinical patients.Besides the inhibition of TGF-β1 may result in inflammation and lead to dead.Therefore it is need baddly to look for a better taget for preventing renal fibrosis,and it is donnot influence the normal physiological function,when we want to cure the renal fibbrosis with blocking the target.Complement 5 is a new factor which can lead to renal fibrosis,it takes part in the progression of the fibrosis of liver,lung etal.Professor PeterBoor etal detected that the degree of renal fibrosis of C5 knocked out mice is lower than normal mice after the mice were been ligated the left ureter.The collagen,fibronectin,smooth muscle actin,Vimentin and infiltrative macrophages were much lower especical during the nonage of obstruction(from 5^th to 10^th).So he thinks that C5 may be a new factor for promoting the process of renal fbrosis,and it may been thougt a new target for preventing and curing renal fibrosis.Complement fragment 5a receptor(C5aR) is an important element in the systerm of Complement,which are been expressed ubiquitously on a wide variety of cells but particularly on the surface of immune cells like macrophages,neutrophils and T cells,and produce its effect by binding with C5a.Recently,it is been detected that C5aR was been expressed on the epithelium of proximal convoluted tubule for normal human,and take part in the progress of renal fibrosis.Protein C Which was be filtrated by glomerular and produced by renal can produce lots of factors which can promote the progrecess of renal fibrosis by binding with C5a in the Experimental Animal Models which was maded by unilateral ureteral obstruction(UUO)and lead to proteinuria.However,The effect and mechanism of C5aR are not clear in the Experimental Animal Models which is nonalbuminuric.PeterBoor etal is the first person who reports that the degree of renal fibrosis was decrease obviously in the C5 knockedout mice following UUO.It is not clear that the role of C5aR in the Experimental Animal Models of UUO. Complement system play damaging and protecting role in kidney disease.Stefan P.Berger etaldiscovered that the upper stream of complement system plays a benificial effect,and the downstream plays a adverse effect.The inhibitorof C5 can interrupt the progression of brightic and the production of membrane attack complex,doesnot affect the effect of upper stream.If we make use of the inhibitor of C5 and C5aR,we can block the progression of renal fibrosis and relieve the degree of renal fibrosis.It is very positive for the reserch of blocking renal fibrosis.The Experimental Animal Models which was been made by UUO was been accepted by most reserchers who were studying the mechanism of renal fibrosis.We are going to reserch the expression of C5aR and TGF-β1 on the mice after UUO and investigate the relation between C5aR and TGF-β1 during the progression of renal fibrosis.We hope we can get a new thread to cure the renal fibrosis and provid some benificial conclusion which can explain the mechanism of renal fibrosis.Object1,To study the expression ofå’ŒTGF-β1 in SD rats with Unilateral Ureteral Obstruction(UUO)and the relation between C5aRå’ŒTGF-β1 following UUO.2,To reserch the role of C5aR during the progreession of renal fibrosis following UUO.Methods1,Thirty six male Sprague-Dawley(SD) rats were randomly subdivided into a sham-operated group,and UUO group.UUO model was induced by ligating the left ureter of rats.Six rats in each group were sacrificed 5^th,10^th,15^th days after UUO.2,Pathological changes of the renal tissue were observed by HE and Masson staining, the protein expressions of C5aR,TGF-beta1 were detected by immunohistochemical staining.3,The SPSS(version 13.0) software packages were used for the statistical analysis.We use factorial analysis to analyse the results and use correlation and Partial analysis to analysis the correlation between the rate of positive areas of TGF-β1 C5aR and renal tubulointerstitial injury index,All the analyses used two-tailed probability.Given the possible risk of Typeâ… error,significant results must be considered with caution when P-values are marginally₀.05.Results1,At the 5^th day,there was renal tubular ectasia,interstitial cells were partialy denaturated in the UUO group.when getting the 10th day,we found necrosis of interstitial cells in renal tubule and an increase of fiber in interstitial substance.While at the 15^th day,there was asystematic thickening and shrinkage of renal tubular basement membrane,and the fibrosis was obvious(p＜0.05).Injure exponent of interstitial substance and the extent of nephritic fibrosis in UUO group were much higher than that in SOR group at different time point respectively(p＜0.05).2,Results of immunohistochemistry indicated that:there was only a little expression of C5aR in nephridial tissue of SOR group's rats.The expression of C5aR in the UUO group at the 5^th,10^th,15^th day[7.94±2.67,12.39±2.64,13.37±0.98]was much higher than that in SOR group[4.50±2.32,5.69±1.73,4.30±1.45](P＜0.05) respectively.In addition,The C5aR's expression at the 10^th day was much higher than that at the 5^th day(P＜0.05),while the increase from the 10^th day to 15^th day was just a little.It is same to be seen on the expressions of TGF-beta1.ConclusionC5aR may take part in renal intersititial fibrosis at the early stage.C5aR play a benifitial role in the kidney by upregulating the TGF-beta1 expression and promoting the renal interstitial fibrosis following UUO,or maybe there was another path which directly lead to renal fibrosi with C5aR bonding C5a.