Renoprotective Effects And Molecular Mechanisms Of Total Saponins From Stems And Leaves Of Panax Ginseng And Ginsenoside Re On Cisplatin-induced Kidney Injury In Mice

Cisplatin(cis-diamminedichhloroplatinum(II),CDDP)is one of the most extensive chemotherapeutic treatment of solid tumors.It has been reported that in high dose of CDDP can inhibit tumor growth and has good clinical effect,but a high dose of CDDP can lead to irreversible renal injury and even death,at present haven't found effective drug can inhibit the side effects.So find a drug CDDP induced renal injury could be restrained effectively is imperative.Total saponins from stems and leaves of Panax ginseng(GSLS)is the total saponins from the processed into the dry stems and leaves of ginseng.Contains a large number of kinds of ginsenosides,and has a variety of biological activities,there have been proved the GSLS has anti-aging,resist fatigue,enhance memory,enhance immunity effects.In this paper,we establish CDDP-induced kidney injury model to evaluate the protective effect of GSLS of renal protective effect.Results show that the GSLS to restore the change of body weight and renal indexes in mice,reduce the mice serum creatinine(CRE),urea nitrogen(BUN),tumor necrosis factor-?(TNF-?),interleukin-1?(IL-1?)level,elevated the content of glutathione(GSH)and the activity of catalase(CAT)in renal tissue;By H&E staining and PAS staining demonstrate GSLS can improve cisplatin causes kidney organization structure change;Hoechst 33258 staining certify GSLS can inhibit cisplatin-induced renal cell apoptosis,at the same time,the results confirmed by the TUNEL staining and Hoechst 33258 staining,and there have a dose dependent relationship.According to the above results show that GSLS CDDP-induced acute renal injury has a protective effect.GSLS contains a lot of ginsenoside Re(G-Re),and G-Re was one of the main type of the triterpenoid saponins,have many biological activities,including the strengthen immunity,restrain central nervous,dilate blood vessels,lower blood pressure,fatigue resistance,and so on.In addition,we establish CDDP-induced acute kidney injury model to evaluate the protective effect of G-Re of renal protective effect.The results show that the Re can restore the change of body weight and renal indexes in mice;Reduced renal function indexes in serum creatinine(CRE)and urea nitrogen(BUN)level in mice;In terms of oxidation stress in renal tissue,reduced the malondialdehyde(MDA)levels and elevated the content of glutathione(GSH)and catalase(CAT)in renal tissue,at the same time in the immunofluorescence staining proved thecytochrome P450(CYP2E1)and 4-hydroxynonenal(4-HNE)expression were suppressed;In terms of inflammation,we used immunohistochemical staining to detect,the result showed that Re treatment decreased cyclooxygenase-2(COX-2)and type induced the expression of nitric oxide synthase(iNOS)expression of kidney tissue.In terms of apoptosis we used Western blot and immunohistochemistry staining to detect,the result shows that G-Re treatment decreased the expression of Bax and Bcl-2,and there is a dose-response relationship,the Hoechst 33258 staining and TUNEL staining further confirms the results;H&E staining results show that G-Re ginsenosides can effectively inhibit the pathological changes of the cellular structure.To sum up,this studies showed that GSLS and G-Re treatment of acute kidney injury induced by CDDP have nephroprotective,the treatment mechanism may include inhibiting oxidative stress,inflammation expression and apoptosis..