الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Acute kidney injury (AKI) is common condition defined by sudden reduction in kidney function that occurs within few hours or days. It is associated with significant mortality, development of chronic kidney disease and end-stage renal disease.
The incidence of AKI in ICUs increased over the past decades in the world, acute kidney injury (AKI) also carries a significant economic impact due to increase the hospitalization costs,
Ischemia/reperfusion (I/R) injury in the kidney is complex patho-physiologic syndrome that occurs in transplantation, hemi nephrectomy and vascular surgery. It consider the common cause of acute kidney injury (AKI) and renal failure.
Ischemia-reperfusion (I/R) characterized by decrease in blood supply to organ, followed by subsequent perfusion and re-oxygenation. Reduced blood flow in organ leads to reduce oxygen and nutrient supply on the one hand, and decreased removal waste product on the other hand.
In response to cellular stress; autophagy is up-regulated and can maintain an adaptive strategy for cell survival. Autophagy involves sequential process that results in the digestion of cellular materials, such as proteins, lipids, and damaged organelles, inside double-membrane vesicles called autophagosomes. These autophagosomes fuse with lysosomes to form autolysosomes for waste elimination, energy generation, and recycling of the cellular components.
The AMPK- signaling pathway was considered an essential regulator of the autophagy during energy depletion. Many studies suggest that autophagy protects the I/R-induced renal tubular cell injury via an AMPK-regulated pathway.
Metformin, a common used antidiabetic therapy and is well-known as AMPK stimulator, and can be used for AMPK/autophagy induction.
Several genes are involved in the generation and maturation of autophagosomes, including autophagy related gene 7(ATG7) and microtubule-associated protein 1 light chain 3 (LC3). They have been widely used as the markers for autophagy. During the autophagic process, LC3 II is involved in the elongation of autophagosome, recruitment of autophagy adaptor proteins, and fusion of autophagosome and lysosome.
ATG7 acts as an E1_like activating enzyme and facilitates both microtubule-associated protein light chain 3 (LC3) fuse with phosphatidylethanolamine(PE), as well as ATG12 conjugation, which play important roles in autophagosome biogenesis in autophagy.
Purpose of the study: The present study aims to assess the impact of metformin for induction of the autophagy process in renal ischemia/reperfusion injury.
Basic procedures; There were three groups of rats; - Control group, the ras in the control group were performed with laparotomy under anesthesia with no treatment (The abdomens in the control group were opened and both kidneys were exposed for (45) min, but renal pedicles were not clipped through surgical procedure, then closed). - Ischemic-reperfusion group, bilateral renal pedicles were clipped for 45 min, followed by perfusion for 24 h to develop I/R model. IR + metformin 300 mg/kg group, rats were pretreated with the AMPK activator metformin (Met) at 300 mg/kg, through oral gavage 12 and 2 hours before 45 min of ischemia. The rats were scarified, blood glucose was measured for all rats, sera were isolated from rats in all groups and used to evaluate the serum creatinine and blood urea nitrogen. RNA was separated for measuring ATG7 gene and LC3II gene expression by RT-PCR and histopathological examination was done for renal tissue in all groups, MDA also was measured.
Our findings: this study has showed significant increase of the kidney parameters including serum Cr and urea in ischemia/reperfusion group compared to control group. Metformin treatment had protective effect in I/R group that receive treatment through up- regulation of autophagy marker ATG7 and LC3II gene & improve kidney function tests.
Conclusion: The results suggested the autophagy that induced by metformin through AMPK pathway has protected kidney from I/R injury.