Effects of glucagon-like peptide-1 receptor agonists on ischemia/reperfusion injury in isolated hearts of rats with metabolic syndrome

[M. P. Ravić]

100 listova

Metabolički sindrom je skup međusobno povezanih poremećaja koji obuhvataju hipertenziju, dislipidemiju, hiperglikemiju, insulinsku rezistenciju i gojaznost. Uprkos brojnim dostupnim lekovima, savremeni vodiči izdvajaju agoniste receptora za peptid sličan glukagonu 1 (glucagon like peptid, GLP-1) kao kamen temeljac u terapiji pacijenata sa metaboličkim sindromom. Glavni cilj ovog istraživanja bio je da se ispitaju efekti primene agonista GLP-1 receptora (liraglutid, eksenatid, dulaglutid i semaglutid) na ishemisjko reperfuzionu povredu izolovanog srca pacova sa metaboličkim sindromom. U istraživanje je uključeno 50 mužjaka pacova Wistar albino soja koje su nakon potvrde indukcije metaboličkog sindroma razvrstani u 5 grupa u zavisnosti od primenjenog leka. Nakon 6. nedelje od početka eksperimentalnog protokola, funkcija srca ispitana je in vivo primenom ultrazvuka. Neposredno nakon žrtvovanja, dekapitacijom, uzeti su uzorci krvi kako bi se odredile vrednosti triglicerida, holesterola, glikemije, insulina, kao i parametri oksidativnog stresa: indeks lipidne peroksidacije - TBARS, nitriti, super oksid anjon radikal, vodonik peroksid, katalaza, superoksid dismutaza, glutation. Funkcija srca ex vivo ispitana je upotrebom Langendorfove tehnike izolovanog srca sisara. Takođe je sprovedena i histomorfološka analiza srca, jetre, bubrega i pankreasa. Rezultati su pokazali da agonisti GLP-1 receptora imaju značajne kardioprotektivne osobine, pošto su poboljšali oporavak i funkcionalne performanse miokarda. Istovremeno, lekovi su ublažili ključne metaboličke poremećaje (hiperglikemija, dislipidemija i hipertenzija). Navedeni efekti su posledica složenog delovanja, koji uključuje antioksidaciona, antiinflamacijska i antiapoptotska svojstva. Rezultati istraživanja ukazuju na korisnost primene agonista GLP-1 receptora kod obolelih od metaboličkog sindroma i cilju prevencije i ublažavanja ishemijske bolesti srca.

Metabolic syndrome is a set of interrelated disorders that include hypertension, dyslipidemia, hyperglycemia, insulin resistance, and obesity. Despite the numerous drugs available, modern guidelines highlight glucagon-like peptide 1 (GLP-1) receptor agonists as the cornerstone in the treatment of patients with metabolic syndrome. The main goal of this study was to examine the effects of the administration of GLP-1 receptor agonists (liraglutide, exenatide, dulaglutide and semaglutide) on ischemia-reperfusion injury in the isolated heart of rats with metabolic syndrome. 50 male Wistar albino rats were included in the research, and after confirmation of the induction of metabolic syndrome, they were classified into 5 groups depending on the drug administered. After the 6th week from the beginning of the experimental protocol, the function of the heart was examined in vivo using ultrasound. Immediately after sacrifice, by decapitation, blood samples were taken to determine the values of triglycerides, cholesterol, glycemia, insulin, as well as parameters of oxidative stress: lipid peroxidation index - TBARS, nitrites, super oxide anion radical, hydrogen peroxide, catalase, superoxide dismutase, glutathione. Ex vivo cardiac function was examined using the Langendorff technique of the isolated mammalian heart. A histomorphological analysis of the heart, liver, kidneys and pancreas was also performed. The results showed that GLP-1 receptor agonists have significant cardioprotective properties, since they improved the recovery and functional performance of the myocardium. At the same time, the drugs alleviated key metabolic disorders (hyperglycemia, dyslipidemia, and hypertension). The mentioned effects are the result of a complex action, which includes antioxidant, anti-inflammatory and antiapoptotic properties. The results of the research indicate the usefulness of GLP-1 receptor agonists administration in patients with metabolic syndrome for the purpose of preventing and mitigating ischemic heart disease.

peptid sličan glukagonu 1, agonisti GLP-1 receptora, metabolički sindrom, ishemijsko reperfuziona povreda, redoks status

glucagon-like peptide 1, GLP-1 receptor agonists, metabolic syndrome, ischemia reperfusion injury, redox status

612.173:599.323.452 599.323.452

Eksperimentalna fiziologija

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