Effect Of Preactivation AMPK By Metformin On Rat Residual Renal Function Following Partial Nepherectomy

Objective: To investigate the effect of metformin pretreatment on rat residual renal function following partial nephrectomy.Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups: sham-operated(Sham), partial nephrectomy(PN), and metformin pretreatment(Met). Before establishing partial nephrectomy model, group Met was administered metformin 300mg?kg-1?d-1 for three days, while group PN was administered equal volume of saline. After three days, blood glucose was testing before surgical procedures, and a right-side nephrectomy was performed on all groups. Then for the sham-operated group, the left renal pedicle was separated without clamping. For the PN and Met groups, the left renal pedicle was blocked with a non-traumatic vascular clamp for 40 min while a lower pole partial nephrectomy was performed. All the kidney specimens and blood samples were collected at 24 hours after reperfusion. Renal function was assessed by serum BUN and Cr levels. The specimens were evaluated by western blot for p-AMPK and AMPK, immunohistochemical staining for p-AMPK, and standard histology. TNF-α was also detected by ELISA in both kidneys and circulation.Results: Metformin pretreatment did not influence the serum glucose. At 24 hours, compared to PN group, metformin pretreatment improved the renal dysfunction induced by partial nephrectomy, although there were no significant differences between group Met and group PN(P>0.05). The cut-face of partial nephrectomy shows similar severe histopathological damage in the Met and PN groups. Metformin pretreatment significantly reduced the renal injury score in group Met compared with that of the PN group(P<0.05). Immunohistochemistry data showed Ampk activation in both Met and PN groups. The western blot analysis revealed that the expressions of p-AMPK in group Met and group PN were significantly higher than that in the Sham group was(P<0.05), while the expression of p-AMPK was much more in group Met than it was in the PN group(P<0.05). Compared to PN group, metformin preconditioning significantly reduced the TNF-α release in both kidneys and circulation(P<0.05).Conclusion: We have demonstrated that metformin pretreatment may attenuate renal injury induced by PN. Inhibition of inflammation through AMPK pathway might be involved in the renoprotective actions.