An Experimental Study About The Effect Of Manshenkangning On Kidney Tissue And The Protein Expression Of SIRT1/COX-2in Renal Interstitial Fibrosis Rats

Objective:To observe the effects of Manshenkangning on the expression of SIRTland COX-2in adenine fed rats and evaluate oxidative stress in kidneys of chronic renalfailure rats, even investigate the mechanism o faction for Manshenkangning on renal interstitial ifbrosis.Methods：Male Wistar rats only60rats, random extraction7rats as normal group, andthe rest to build module only53rats. Adopting Adenine-induced renal failure inrat models，the module rats were randomly divided into5groups: the model group, the losartan group, renal interstitial ifbrosis rats treated with Manshenkangning30mg.kg^-1.d^-1，Manshenkangning15mg.kg^-1.d^-1，and Manshenkangning7.5mg*kg-l*d^-1. Normal group, model control group attain equivalent distilled water （0.5ml/100g） lavage. After30days, the levels of Scr、BUN、24hMTP、eGFR in therenal tissue were all measured. Paraiffn sections were made using routine method，stained with HE、Masson staining and observed with light microscope for histopathological changes，the content of H₂O₂SG GSH i, GSand n the renal tissue were all measured. Immunohistochemistry and Real Time PCR were used to detectthe amount of SIRT1-、COX2protein and mRNA expression。Results：The control group of Serum creatinine（Scr），blood urea nitrogen（BUN），24-hour urine protein（24hMTP） in were signiifcantly higher than that in the normal group，but glomeruar ifltration rate （eGFR）significantly reduced（P<0.01）.Comparedwith the control group, Scr,24hBUN and MTP of Manshenkangning of each treatment group and losartan group decreased signiifcantly，and eGFR increased（P<0.01）. The content of H₂O₂on Manshenkangning were decreased signiifcantly （P<0.05），but the content of GSSG and GSH were increased obviously（P<0.05）.GSSG, GSH，and H₂O₂differences were no statistical signiifcance between Manshenkangningof each treatment group and losartan group （P>0.05）,but high dose group can ma ke GSSG，GSH levels rose significantly, H₂O₂content strikingly reduced. Immunohistochemical and RealTime PCR results showed that the model group SIRT1protein and mRNA expression level than normal group was signiifcantly reduced （P <0.01），and COX-2protein and mRNA expression level than normal group increased signiifcantly, compared with the model group, Manshenkangning of each treatment group and losartan group can increase the SIRT1protein and the expression ofmRNA level, reduce the COX-2protein and mRNA expression level, and both ofthem have the statistically signiifcant difference （P <0.01），including Manshenkangning of high dose group improve the above index more obvious.Conclusions:Manshenkangning has the renal protective effect and can signiifcantly improve the chronic renal failure rat renal function,which the mechanism may through the adjustment SIRTI activity, inhibiting renal COX-2protein expression to control the renal inlfammatory reaction, improve the kidney of antioxidant stress ability, therefore，reducing renal interstitial and delaying the onset and development of chronic renal failure.