The Effect And Its Mechanism Of Ginsenoside Rb1 On The Renal Interstitial Fibrosis In UUO Rats

OBJECTIVE: The renal interstitial fibrosis(RIF) is almost the commonpathway by which all the various chronic kidney diseases (CKD) progess toend stage renal disease(ESRD). Tubular epithelial-myofibroblasttransdifferentiation (TEMT)that various cytokine participate is one ofthe important mechanism of RIF. Mang studies shows in acute renalfailure, oxidative stress play an important role.We investigated theexpression of cytokine in UUO rats and the effects of ginsenoside Rb1 onthese factors. And we examined whether ginsenoside Rb1 can alleviate RIFin vivo.METHODS:Rats were randomly assigned into unilateral ureteralobstruction model group(UUO), ginsenoside Rb1 group (Rb1),ARB-treatedgroup and sham-operated group(SOR).From the first day after initial UUO,ARB groups were intraperitoneal injected at losartan 20mg/kg every day.UUO, Rb1 and SOR groups were intraperitoneal injected at identicalvoluminal normal saline. Rb1 groups were intraperitoneal injected atginsenoside 50mg/kg.d every day. UUO,ARB and SOR groups wereintragastric administrated at identical voluminal normal saline. At 3,7,14,21,28days after UUO, 5 rats selected randomly from each group werekilled.The levels of 24-hour urine protein, serum creatinine were examined ateach time point. We scored the degree of tubulointerstitial damage anddetected the protein expression of CTGF, a-SMA, TGF-β1,FN and ColⅠbyimmunOH·istochemitry staining and Western blot. The levels of a-SMA,TGF-β1 and CTGF mRNA were examined by real-time reversetranscription-polymerise chain reaction(RT-PCR) and westernblot(WB).RESULT:①There were no significant difference in the level of 24-hoururine protein among each group. (P＞0.05)②The level of serum creatininein UUO group was obviously higher than other groups at day 3,7,14(p＜0.05).Compared with the UUO group, the level of serum creatinine was decreasedobviously in the Rb1 treatment group.There were no difference in the level ofserum creatinine among each group at day 21,28.③Compared with the UUOgroup at day 3,7,14, the level of OH·,MDAwas decreased obviously in theRb1 treatment group(p＜0.05). Inversely the level of SOD was obviouslyincreased(p＜0.05), The effect was similar in ARB-treated group.Therewere no difference in the level of OH·,MDA,SOD among each group atday 21,28.④The renal tubulointerstitial damnification and inflammatorycell soakage were more severe in UUO than those in other groups(p＜0.05),they were decreased obviously in the Rb1 treatment group(p＜0.05).⑤theexpression levels of TGF-β1,CTGF,a-SMA,ColⅠ,FN in UUO werehigher than that in other groups(p＜0.05).,they were decreased obviously inthe Rb1 treatment group(p＜0.05). The effect was similar in ARB-treatedgroup.⑥Compared with the UUO group, the levels of TGF-β1,CTGF,a -SMA mRNA and protein were significantly increased in Rb1 treatmentgroup (p＜0.05), The effect was similar in ARB-treated group.CONCLUSION:1.It exists oxidative stress in UUO, oxidative stress can activateTGF-β1/CTGF signal pathway and cause renal interstitial fibrosis.2. Rb1 can improve validly renal interstitial fibrosis by impede the progressof TEMT and decreasing ECM.3.The effect of Rb1 is associated with oppose oxidative stress andinterfere in TGF-β1/CTGF signal pathway.