Title (srp)

Uticaj minociklina na ishemijsko/reperfuzionu povredu izolovanog srca hipertenzivnih i dijabetičnih pacova

Author

Šobot, Nikola, 1982-

Contributor

Jakovljević, Vladimir, 1971-
Miloradović, Vladimir, 1971-
Škrbić, Ranko, 1961-
Srejović, Ivan, 1985-

Description (eng)

ntroduction: Coronary artery disease is one of the most common heart diseases and is theleading cause of morbidity and mortality worldwide. Myocardial damage in acute myocardialinfarction occurs due to arterial occlusion that causes ischemia, while subsequent reestablishment of blood flow can result in reperfusion injury. Much effort has been made inpharmacological therapy and prevention of ischemic/reperfusion injury over the past twodecades to find the most effective agent that could reduce morphological and functionalmyocardial damage after ischemia and reperfusion. The positive pleiotropic effects ofminocycline are attributed to various mechanisms including anti-inflammatory, antioxidant andantiapoptotic effects, as well as inhibition of metalloproteinases.Objective: Investigation of the effects of preconditioning and postconditioning withminocycline on functional and morphological recovery of rat heart after ischemic/reperfusionmyocardial injury with special attention to conditions of type 2 diabetes and hypertension.Methods: The study included 72 male rats (Wistar albino strain, body weight 250 ± 20 g, age8 weeks). Rats were classified into groups based on the presence of type 2 diabetes orhypertension as well as on one of the types of minocycline conditioning: preconditioning withminocycline at a dose of 1µM or postconditioning with minocycline at the same dose. Type 2diabetes was induced by a high-fat diet and streptozotocin at a dose of 25 mg/kg body weight.Spontaneously-hypertensive rats were used for the experimental model of hypertension.Isolated hearts were perfused by retrograde Langendorf perfusion. For ischemia, a 20-minutemodel of global ischemia was used, followed by a 30-minute reperfusion. Coronary flow valueswere determined fluometrically, and left ventricular function parameters (dp/dt max, dp/dt min,SLVP, DLVP and HR) were continuously monitored. In the coronary venous effluent samplesof rat heart, oxidative stress parameters were determined by spectrophotometric methods, andchanges in the heart were examined by standard histological analysis.Results: The results of this study indicate the undoubted protective effects of minocycline inconditions of experimentally induced ischemia and reperfusion in the hearts of rats withinduced type 2 diabetes and in the hearts of spontaneously hypertensive rats. The analysis ofthe obtained results related to the dynamics of production of biomarkers of oxidative stressleads to the conclusion that the antioxidant potential of minocycline and reduction of oxidativedamage certainly makes important, if not the key mechanism of protective action ofminocycline.

Description (srp)

Uvod: Koronarna bolest arterija je jedna od najčešćih bolesti srca i glavni je uzrokobolevanja i smrtnosti širom sveta. Oštećenje tkiva miokarda u akutnom infarktumiokarda nastaje upravo zbog arterijske okluzije koja uzrokuje ishemiju dok naknadnouspostavljanje ponovnog protoka krvi može da rezultira reperfuzijskom povredom. Ufarmakološkoj terapiji i prevenciji ishemijsko/reperfuzione povrede tokomprethodne dve decenije učinjeno je mnogo napora kako bi se pronašao što efikasnijiagens koji bi mogao da umanji morfološka i funkcionalna oštećenja miokarda nakonishemije i reperfuzije. Pozitivni plejotropni efekti minociklina pripisuju serazličitim mehanizmima uključujući antiinflamacijsko, antioksidaciono iantiapoptotsko dejstvo, kao i inhibicija metaloproteinaza.Cilj: Ispitivanje efekata prekondicioniranja i postkondicioniranja minociklinomna funkcionalni i morfološki oporavak srca pacova nakon ishemijsko/reperfuzionepovrede miokarda sa posebnim osvrtom na uslove dijabetesa tipa 2 i hipertenzije.Metode: Istraživanje je obuhvatilo 72 pacova muškog pola (Wistar albino soj, telesnemase 250±20 g, starosti 8 nedelja). Pacovi su svrstani u grupe na osnovu prisustvadijebetesa tipa 2 ili hipertenzije kao i na osnovu nekog od tipa kondicioniranjaminociklinom: prekondicioniranje minociklinom u dozi od 1µM ilipostkondicioniranje minociklinom u istoj dozi. Dijabetes tip 2 indukovan jeprimenom ishrane bogate mastima i streptozotocina u dozi od 25 mg/kg telesne mase.Za eksperimentalni model hipertenzije koristili su se sponatno-hipertenzivnipacovi. Izolovana srca su perfundovana metodom retrogradne perfuzije poLangendorfu. Za ishemiju je upotrebljen model globalne ishemije u trajanju od 20minuta kojoj sledi reperfuzija u trajanju od 30 minuta. Vrednosti koronarnog protokasu određivane floumetrijski, a parametri funkcije leve komore (dp/dt max, dp/dt min,SLVP, DLVP i HR) su kontinuirano praćeni. U uzorcima koronarnog venskog efluentasrca pacova spektrofotometrijskim metodama su određivani parametri oksidacionogstresa, a standardnom histološkom analizom ispitivane su promene na srcu.Rezultati: Rezultati ovog istraživanja ukazuju na nesumnjive protektivne efekteminociklina u uslovima eksperimentalno indukovane ishemije i reperfuzije kako nasrcima pacova sa indukovanim dijabetesom tipa 2, tako i na srcima spontanohipertenzivnih pacova. Analizom dobijenih rezultata koji se odnose na dinamikuprodukcije biomarkera oksidacionog stresa izvodi se zaključak da antioksidacionipotencijal minociklina i redukcija oksidacionog oštećenja svakako čini važan, akone i ključni mehanizam protektivnog dejstva minociklina.Ključne reči: minociklin, ishemija, reperfuzija, dijabetes tip 2, hipertenzija,oksidacioni stres

Description (srp)

-

Object languages

Serbian

Date

2022

Rights

Creative Commons License
This work is licensed under a
CC BY-NC-ND 3.0 AT - Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode

Identifiers