Abstract

Hyperglycemia present in diabetes mellitus is responsible for the increase of ATP, an agonist for P2X7 receptor. Activation of this receptor promotes the opening of channels and pores in the plasmatic membrane, leading to the release of cytokines and/or cell death and it is considered among the causes of DN. The aim of this study was to evaluate the P2X7 in the progression of DN and its correlation with inflammatory markers in rats kidneys. Male adult Wistar rats were alocated into 2 groups: DM received streptozotocin for diabetes induction; CTL received vehicle. At 5th, 6th, 7th and 8th weeks after diabetes induction, glycemia and body weight were evaluated, the animals were euthanized and the remaining kidney was collected for P2X7, IL-6 and IL-10 analysis by Western blotting and histology. Statistical analysis: we utilized unpaired Student's t test, and correlations were made by Spearman test, using GraphPad Prism 5.0. DM group glycemia was elevated in all weeks of diabetes and weight was reduced vs CTL. P2X7 was significantly increased in DM in all weeks analyzed. IL-6 increased progressively until the 8th week, vs CTL; IL-10 showed a gradual decrease with disease progression. Significant positive correlation was demonstrated between P2X7 and glycemia during the 7th and 8th weeks of diabetes; there was a moderate and positive correlation with P2X7 and IL-6. In the histology, the DM group presented inflammatory infiltrate, interstitial fibrosis and processes of tubular degeneration/regeneration from the 5th to 8th weeks after diabetes induction. Our findings show that P2X7 is increased in the evolution of diabetes and it is correlated with inflammation. Further studies are needed to assess whether inactivation of this receptor could be a therapeutic target in the management of diabetic nephropathy.