The Renoprotective Effects Of Ginsenoside On ARF Rats Via Upregulating The Expression Of HIF-1? In Hypothalamus And Kidney

Objective: In the present study,we investigated the renal protective effect of ginsenoside(GS)administrated orally on acute renal failure(ARF)in rats and its correlation with the changes of hypoxia-inducible factor-1?(HIF-1?)and its target gene vascular endothelial growth factor A(VEGF-A)both in hypothalamus and in kidney.Methods: Male SD rats were randomly divided into four groups,ARF+physiological saline(NS)(0 h,6 h,12 h,24 h and 48 h)group,ARF+GS(0 h,6 h,12 h,24 h and 48 h)group,NS+NS(0 h,6 h,12 h,24 h and 48 h)group and NS+GS(48h)group.Glycerol-induced acute renal failure in rats was employed.Blood urea nitrogen(BUN)and creatinine(Cre),were measured by commercial regents,as well as malondialdehyde(MDA),superoxide dismutase(SOD)in renal cortex homogenate and hypothalamic homogenate by experiment in vivo.Histopathological changes in the kidney were observed by HE staining.Meanwhile,the expression of HIF-1? and VEGF-A in the kidney and hypothalamus were observed by Western Blot.The expression of HIF-1-IR in the proximal convoluted tubule(PCT)was also observed by immunohistochemistry.Results: 1.BUN and Cre were significantly increased in ARF rats treated with natural saline for 48 h(ARF+NS group)(P?0.05),but decreased in ARF rats treated with ginsenoside for 48 h(ARF+GS group)(P?0.05).2.ARF+NS group showed a severe tubular necrosis;but ARF+GS group displayed a better recovery.3.There were an increase of MDA and a decrease of SOD in renal cortex and hypothalamus in ARF+NS group(P ? 0.05),but both of them were reversed in ARF+GS group(P<0.05).4.Western blot showed an obvious increase of expression of HIF-1?-IR in kidney in ARF+NS(6 h,12 h,24 h and 48 h)groups(P?0.05),the expression of HIF-1?-IR was further significantly enhanced in ARF+GS groups,compared with both ARF+NS and NS+NS groups at 6 h,12 h,24 h and 48 h(P?0.05).5.Western blot showed an obvious increase of expression of HIF-1?-IR in the hypothalamus in ARF+NS(6 h,12 h,24 h and 48 h)groups(P?0.05),the expression of HIF-1?-IR was further significantly enhanced in ARF+GS groups,compared with ARF+NS groups at 24 h and 48 h(P?0.05).6.Western blot showed an obvious increase of expression of VEGF-A-IR in kidney in ARF+NS(6 h,12 h,24 h and 48 h)groups(P?0.05),the expression of VEGF-A-IR was further significantly enhanced in ARF+GS groups,compared with ARF+NS groups at 6 h,12 h and 48 h(P?0.05).7.Western blot showed an obvious increase of expression of VEGF-A-IR in the hypothalamus in ARF+NS(6 h,12 h,24 h and 48 h)groups(P?0.05),the expression of VEGF-A-IR was further significantly enhanced in ARF+GS groups,compared with both ARF+NS and NS+NS groups at 6 h,12 h,24 h and 48 h(P?0.05).8.Immunohistochemistry showed an obvious increase of HIF-1?-IR in the PCT in ARF+NS 6 h group(P?0.05)and in ARF+NS 48 h group(P?0.05),but HIF-1?-IR was further enhanced in ARF+GS 6 h group and ARF+GS 48 h group,compared with ARF+NS groups at 6 h and 48 h.(P?0.05).Conclusion: Our results indicated that ginsenoside could markedly improve renal function in ARF rats by oral administration,and increase antioxidative effects,preventing renal damage.Our findings strongly suggested that ginsenoside may have a renal protective effect against acute renal failure induced by glycerol.The expression of HIF-1? and VEGF-A in kidney was upregulated in ARF rats.Our results also indicated that ginsenoside administrated orally could further enhance the expression of HIF-1? and VEGF-A in the kidney throughout the period of the study.And the expression of HIF-1? and VEGF-A in the hypothalamus was similar to that in the kidney.Consequently,we provided a new evidence that the upregulation of HIF-1? in kidney and hypothalamus contributed to the renal protective effects of ginsenoside against acute renal failure via regulating the downstream of its target gene VEGF-A.