Effects and Mechanisms of Metformin Preconditioning on Renal Ischemia-reperfusion Injury in Rats / 医学研究杂志

ABSTRACT

Objective To investigate the effects of metformin preconditioning on renal ischemia-reperfusion injury in rats and its possible mechanism.Methods A total of 30 rats which were healthy adult male SD rats weighing 220-250g were randomly divided into 3 groups randomly (n =10)sham operation group (Sham group),ischemia reperfusion group (I/R group) and metformin group (Metformin + I/R group).Group metformin + I/R was given intraperitoneal injection of metformin 0.125mg/(kg · d) before the establishment of I/R model,14days,while Sham group and I/R group were given equal amount of normal saline.After the end of administration,I/R group and metformin + I/R group used the mnethod of removing the right kidney,clamping the left renal artery and vein 45min after the recovery of perfusion to prepare the rat model of renal ischemia and reperfusion.In Sham group,resection of the right kidney was performod,without clamping the left renal artery and vein.Determination of serum creatinine in the blood from inferior vena cava at 24h after reperfusion (Cr) and urea nitrogen (BUN) concentration was performed.Then the rats were sacrificed.Renal tissue morphology,immunohistochemical expression of Bcl-2,Bax and caspase-3 were observed under light microscope.At the same time,Tunel staining were used to evaluate the degree of renal tubular epithelial cell apoptosis.Results Compared with sham group,BUN and Cr in the I/R group and metformin + I/R group were significantly higher than those in the sham group,while the BUN and Cr in the Metformin + I/R group were significantly lower than those in the I/R group,and the difference was statistically significant (P ＜ 0.05).Immunohistochemistry showed that,compared with Sham group,in I/R group and metformin + I/R group,the expression of Bcl-2,Bax and caspase-3 increased significantly.Compared with I/R group,in metformin + I/R group,caspase-3 and bax expression decreased significantly,while the expression of Bcl-2 was stronger than I/R group.Tunel results showed that compared with Sham group,I/R metformin + I/R group and the number of apoptosis of renal tubular epithelial cells was significantly increased in metformin + I/R group.At the same time,the apoptosis of renal tubular epithelial cells was significantly less than I/R group,and the difference was statistically significant.Conclusion Metformin pretreatment can improve renal damage in rats with renal ischemia-reperfusion injury,which may be related to the inhibition of renal tubular epithelial cell apoptosis.