The Mediation Of Hypothalamic MAPK Pathway And Protective Effect Of Ginsenoside Against Acute Renal Failure

Objective:In the present study, we investigated the renal protective effect of ginsenoside administrated orally on acute renal failure in rats mediated by hypothalamic MAPK pathway and its correlation with the changes of choline acetyl transferase in hypothalamus and renal tubular epithelial cell.Methods:Male SD rats were randomly divided into four groups, ARF+NS group, ARF+GS group, NS+NS group and NS+GS group. Glycerol-induced acute renal failure in rats was employed. Blood urea nitrogen and Creatinine were measured by commercial regents, as well as malondialdehyde, reduced glutathione hormone and nitric oxide in renal cortex homogenate by experiment in vivo. Renal histopathological changes were measured by HE stain. Meanwhile, the changes of ChAT-IR in the PCT were observed by immunohistochemistry; the expression of p-ERK1/2 and ChAT in the hypothalamus were observed by Western Blot.Results:1.Glycerol-induced ARF rats treated with NS (2ml) for 48h (ARF+NS group) showed a significant increase in BUN and Cre (P< 0.05). However, Glycerol-induced ARF rats treated with GS for 48h (ARF+GS group) showed a significant decrease in BUN and Cre(P< 0.05).2.In ARF+NS group, severe tubular necrosis was observed, but not in ARF+GS group.3.In ARF+NS group, the level of MDA in renal cortex homogenate significantly increasd (P<0.05), but GSH markedly decreased (P<0.05). However, in ARF+GS group the level of MDA in renal cortex homogenate significantly decreased, but GSH markedly increased (P<0.05).4.Immunohistochemistry showed an obvious increase of ChAT-IR in the PCT in ARF+NS group(P<0.05),but ChAT-IR was further enhanced in ARF+GS group, compared with that in ARF+NS group(P<0.05).5. Western blot showed an obvious increase of expression of ChAT in renal cortex in ARF+NS group(P<0.05), but the expression of ChAT was further enhanced in ARF+GS group, and also compared with that in ARF+NS group(P<0.05).6. Western blot showed an obvious increase of expression of ChAT in the hypothalamus in ARF+NS group(P<0.05), but the expression of ChAT was further enhanced in ARF+GS group, compared with that in ARF+NS group(P<0.05).7.The expression of p-ERK1/2 was increased in the hypothalamus in ARF+NS group(P<0.05), but the expression of p-ERK1/2 was further enhanced in ARF+GS group, and also compared with that in ARF+NS group(P<0.05).Conclusion:Our results indicated that ginsenoside administrated orally in glycerol-induced ARF rats significantly improved renal function, decreased the severity of tubular necrosis, increased antioxidative effects and prevented renal damage. These findings suggested that ginsenoside may have a strong renal protective effect against glycerol-induced acute renal failure. The activity of hypothalamic cholinergic neurons was increased and MAPK pathway was activated; simultaneously ChAT-IR in the PCT was also increased in ARF rats.Our results also indicated that ginsenoside administrated orally could further enhance this effect in ARF rats. Consequently, we provided a new evidence that MAPK signaling pathway and cholinergic neuron in the hypothalamus contributed to renal protective effect of ginsenoside against acute renal failure. This may be one of the central mechanisms of ginsenoside against acute renal failure. The further upregulation of cholinergic activity in the PCT may be one of the peripheral mechanisms of ginsenoside against acute renal failure.