Papel da irisina na renoproteção contra lesões derivadas de isquemia e reperfusão renal bilateral

Abstract

Renal injury due to ischemia and reperfusion (I/R) generates cellular damage that can compromise homeostasis due to the increase in reactive oxygen species, generating local inflammatory processes, hyperplasia and renal hypertrophy. Irisin is a peptide hormone with several physiological actions such as improving energy metabolism, promoting cardiovascular health by reducing inflammation and consequently the risks of hypertension and atherosclerosis, and reducing inflammation in obese and diabetic individuals by improving insulin resistance. Irisin is a mediator of bone health and a protective agent against neurodegenerative diseases. The aim of this study was to evaluate the role of irisin in renoprotection against lesions derived from bilateral renal ischemia and reperfusion. Male Wistar rats were divided into 4 experimental groups (n=6): sham-operated group (SHAM), sham-operated + irisin group (SHAM+IRI), ischemia and reperfusion group (I/R) and ischemia and reperfusion + irisin group (I/R+IRI). The animals were anesthetized and received saline solution or 10nM irisin via the jugular vein. 30 minutes later, they were positioned in lateral decubitus for induction of ischemia and reperfusion. An incision was made in the dorsal wall to access the right and left kidneys. The adipose tissue of the kidneys of each animal was dissected for better visualization of the renal hilum. Ischemia was performed using 30g non-traumatic clamps (Roca Instrumental ®, São Paulo, Brazil) in the specific groups described above; the animals were subjected to 1 hour of bilateral renal ischemia. Twenty-four hours after reperfusion, changes in renal function and histopathology were assessed by calculating the urinary flow rate over a 24-hour period and the glomerular filtration rate, calculated through creatinine clearance. Creatinine and urea levels were measured using the CREATININE PP Kit (Gold Analisa®) and UREA (Gold Analisa®). The biological markers IL-6, IL-1β, NOX4 and HIF-1α were assessed by Western Blotting and VEGF, PGC1-α, eNOS, TNF-α and HIF-1α were assessed by real-time PCR. Renal function and tubular structure assessed by histopathology identified tissue preservation with irisin infusion in the I/R+IRI group. No change in the protein expression of IL-6, IL-1β, NOX-4 and HIF-1α was detected between the groups. eNOS mRNA levels were not significantly altered, but an increase in TNF-α was observed in treated animals and a reduction in the accumulation of HIF-1α, PGC1-α and VEGF in the I/R and I/R+IRI groups compared to the SHAM group. Irisin 10 nM was able to improve renal function and the renal tubular injury score in animals subjected to bilateral ischemia and reperfusion, regardless of HIF-1α, VEGF and PGC1-α, essential pathways in the response to tissue damage. Thus, irisin was able to mediate the response to apoptosis and inflammation through compensatory mechanisms.