Naslov (srp)

Efekti modulacije translokatornog proteina i NO sintaze na funkcionalne i biohemijske promene srca u eksperimentalnom modelu infarkta miokarda izazvanog izoprenalinom : doktorska disertacija

Autor

Ilić, Ana P., 1987-

Doprinosi

Matić, Marija, 1975-
Đurić, Dragan, 1961-
Milovanović, Branislav, 1962-
Ćelić, Vera, 1960-
Jakovljević, Vladimir, 1971-

Opis (eng)

Objective: Investigation of the effects of TSPO protein modulators, PK-11195, and 4'-ClDzp, as wellas NO synthase inhibitor, L-NAME, on cardiometabolic parameters, parameters of oxidative stressand inflammation, biochemical biomarkers in serum and plasma, as well as pathohistological changesin the heart in rats with isoprenaline (ISO)-induced myocardial infarction (MI).Material and methods: The research was conducted over 3 consecutive days. Male Wistar albinorats were randomly divided into eight groups (eight to ten animals in each group): control group (K,saline solution 0.9% NaCl (saline) 0.2 mL subcutaneously (sc.) twice at an interval of 24h),experimental group I (ISO, 85 mg/kg body weight (b.w.) in 1 mL saline solution, sc. twice at aninterval of 24h), experimental group IFR (ISO, 85 mg/kg b.w. in 1 mL saline solution, sc. twice at aninterval of 24h plus saline 0.5 mL intraperitoneally (ip.), experimental group ILN (ISO, 85 mg/kgbody weight in 1 mL saline solution, sc. twice at an interval of 24h plus L-NAME, 50 mg/ kg b.w. insaline ip.), experimental group IP (ISO, 85 mg/kg b.w. in 1 mL saline solution, sc. twice at an intervalof 24h plus PK-11195, 5 mg/kg b.w. in saline ip.), experimental group IPLN (ISO, 85 mg/kg b.w. in1 mL saline solution, sc. twice at an interval of 24h plus PK-11195, 5 mg/kg b.w. in saline ip. plus LNAME,50 mg/ kg b.w. in saline ip.), experimental group IC (ISO, 85 mg/kg b.w. in 1 mL salinesolution, sc. twice in an interval of 24h plus 4'ClDzp, 0.5 mg/kg body weight. in saline i.p.),experimental group ICLN (ISO, 85 mg/kg b.w. in 1 mL saline, sc. twice at an interval of 24h plus4'ClDzp, 0.5 mg/kg b.w. in saline ip. plus L-NAME, 50 mg/kg b.w. ip.). Cardiometabolic biomarkerswere determined in the serum: concentration of high-sensitivity troponin T (hsTnT), the activity oflactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), theconcentration of homocysteine (Hcy), total cholesterol (TH), high-density lipoprotein (HDL),triglyceride (TG), hemostatic biomarkers in plasma: concentration of fibrinogen (FIB) and vonWillebrand factor (vWF); as well as hepato-renal-pancreatic serum biomarkers: concentration of urea,creatinine, uric acid (MC), total protein, albumin, the activity of alanine aminotransferase (ALT),alkaline phosphatase (ALP) and alpha-amylase (α-AMY), and markers inflammation: interleukin 1(IL-1), interleukin 6 (IL-6), interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-α).Oxidative stress parameters were determined in the heart tissue homogenate: activity of glutathioneperoxidase (GPx) and superoxide dismutase (SOD), glutathione concentration, and total Sglutathionylationprotein. In addition, heart tissue was used for pathohistological analysis.Results: Application of isoprenaline led to the occurrence of diffuse transmural infarction, increasedconcentrations of hsTnT and Hcy, a significant decrease in body weight, and an increase in thecardiosomatic index (KSI), and decreased the concentration of LDH and AST. The application ofISO led to an increase in the concentration of FIB, and a decrease in the concentration of TH, HDL,and TG. CK and vWF were not affected by ISO administration, as well as parameters of renalfunction, uric acid (MC), urea, and creatinine. Serum albumin concentration was increased, while TPconcentration was decreased after ISO application. Application of ISO was accompanied by changesin inflammation markers, an increase in the concentration of TNF-α, and a decrease in theconcentration of IL-10, while the concentrations of IL-1β and IL-6 remained unchanged after theapplication of ISO. GPx and SOD activity as well as glutathione concentration had no significantchanges after ISO administration. Total S-glutathionylation was increased by ISO administration. Thejoint administration of PK-11195 and L-NAME increased the concentration of hsTnT, AST, Hcy,TH, FIB, creatinine, MK, UP, IL-10, and SOD, and decreased the concentration of LDH, HDL, urea,ALB, TNF-α, IL- 6 and GPx. The effects of PK-11195 were reflected in a decrease in hsTnTconcentration and an increase in Hcy concentration, changes in lipid status and parameters of hepatorenal-pancreatic function as well as markers of inflammation, certain parameters of oxidative stressand hemostatic parameters. Also, the administration of PK-11195 did not show significantpathohistological changes in heart tissue...

Opis (srp)

Cilj: Istraživanje efekata primene modulatora TSPO proteina, PK-11195 i 4’-ClDzp kao i inhibitoraNO sintaze, L-NAME, na kardiometaboličke parametre, parametre oksidativnog stresa i inflamacije,biohemijske biomarkere u serumu i plazmi, kao i patohistološke promene na srcu kod pacova sainfarktom miokarda (MI) indukovanim izoprenalinom (ISO).Materijal i metode: Istraživanje je sprovedeno tokom 3 uzastopna dana. Mužjaci pacova soja Wistaralbino su raspodeljeni nasumično u osam grupa (osam do deset životinja u svakoj grupi): kontrolnagrupa (K, fiziološki rastvor 0,9% NaCl (f.r.) 0,2 mL subkutano (s.c.) dva puta u intervalu od 24 h),eksperimentalna grupa I (ISO, 85 mg/kg telesne mase (t.m.) u 1 mL fiziološkog rastvora, s.c. dva putau intervalu od 24 h), eksperimentalna grupa IFR (ISO, 85 mg/kg t.m. u 1 mL fiziološkog rastvora,s.c. dva puta u intervalu od 24 h i f.r. 0,5 mL intraperitonealno (i.p.)), eksperimentalna grupa ILN(ISO, 85 mg/kg t.m. u 1 mL fiziološkog rastvora, s.c. dva puta u intervalu od 24 h i L-NAME, 50mg/kg t.m. u f.r. intraperitonealno (i.p.)), eksperimentalna grupa IP (ISO, 85 mg/kg t.m. u 1 mLfiziološkog rastvora, s.c. dva puta u intervalu od 24 h, i PK-11195, 5 mg/kg t.m. u f.r., i.p.),eksperimentalna grupa IPLN (ISO, 85 mg/kg t.m. u 1 mL fiziološkog rastvora, s.c. dva puta uintervalu od 24 h, PK-11195, 5 mg/kg t.m. u f.r., i.p., i L-NAME, 50 mg/kg t.m. u f.r. i.p.),eksperimentalna grupa IC (ISO, 85 mg/kg t.m. u 1 mL fiziološkog rastvora, s.c. dva puta u intervaluod 24 h, i 4’-ClDzp, 0,5 mg/kg t.m. u f.r., i.p.), eksperimentalna grupa ICLN (ISO, 85 mg/kg t.m. u 1mL fiziološkog rastvora, s.c. dva puta u intervalu od 24 h, 4’-ClDzp, 0,5 mg/kg t.m. u f.r., i.p. i LNAME,50 mg/kg t.m. u f.r. i.p.). Određivani su kardiometabolički biomarkeri u serumu:koncentracija visoko senzitivnog troponina T (hsTnT), aktivnost laktat dehidrogenaze (LDH), kreatinkinaze (CK), aspartat aminotransferaze (AST), koncentracija homocisteina (Hcy), ukupnogholesterola (TH), lipoproteina velike gustine (HDL), trigilicerida (TG); hemostatski biomarkeri uplazmi: koncentracija fibrinogena (FIB) i von Wilebrandovog faktora (vWF); kao i hepato-renalnopankreatičnibiomarkeri u serumu: koncentracija uree, kreatinina, mokraćne kiseline (MK), ukupnihproteina, albumina, aktivnost alanin aminotransferaze (ALT), alkalne fosfataze (ALP) i alfa amilaze(α-AMY) i markeri inflamacije: interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 10 (IL-10) ifaktor nekroze tumora alfa (TNF-α). U homogenatu tkiva srca određivani su parametri oksidativnogstresa: aktivnost enzima glutation peroksidaze (GPx) i superoksid dismutaze (SOD), koncentracijaglutationa, i ukupna S – glutationilacija proteina. Pored toga, za patohistološku analizu korišćeno jetkivo srca.Rezultati: Aplikovanje izoprenalina je dovelo do pojave difuznog transmuralnog infarkta sapovećanim koncentracijama hsTnT i Hcy, značajnim smanjenjem telesne mase i povećanjemkardiosomatskog indeksa (KSI), i smanjilo je koncentraciju LDH i AST. Primena ISO je dovela dopovećanja koncentracije FIB i smanjenja koncentracije TH, HDL i TG. Primena ISO nije uticala naCK i vWF, kao i na parametre bubrežne funkcije, mokraćne kiseline (MK), uree i kreatinina.Koncentracija albumina u serumu je bila povećana, dok je koncentracija TP bila smanjena nakonaplikacije ISO. Primena ISO je bila praćena promenama u markerima inflamacije, povećanjemkoncentracije TNF-α i smanjenjem koncentracije IL-10, dok su koncentracije IL-1β i IL-6 ostalenepromenjene nakon primene ISO. Aktivnost GPx i SOD kao i koncentracija glutationa nije imalaznačajne promene nakon primene ISO. Ukupna S-glutationilacija je bila povećana usled primene ISO.Zajednička primena PK-11195 i L-NAME povećala je koncentraciju hsTnT, AST, Hcy, TH, FIB,kreatinina, MK, UP, IL-10 i SOD, a smanjila je koncentraciju LDH, HDL, uree, ALB, TNF-α, IL-6 iGPx. Efekti PK-11195 su se odrazili na smanjenje koncentracije hsTnT i povećanje koncentracijeHcy, promene u lipidnom statusu i na parametre hepato-renalno-pankreatične funkcije kao i namarkere inflamacije, određene parametre oksidativnog stresa i hemostatske parametre. Takođe,primena PK-11195 nije pokazala značajnu patohistološku promenu u tkivu srca...

Opis (srp)

Medicina - Fiziološke nauke / Medicine- Physiological sciences Datum odbrane: 24.10.2024.

Jezik

srpski

Datum

2024

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-ND 3.0 AT - Creative Commons Autorstvo - Bez prerada Austria License.

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

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Fiziologija

infarkt miokarda, izoprenalin, 4’-ClDzp, PK-11195, L-NAME, metabolizam srca, biohemijski markeri, oksidativni stres, markeri inflamacije, veličina infarktnog polja, pacov

612.176:616.127-005.8(043.3)

OSNO - Opšta sistematizacija naučnih oblasti, Fiziologija

myocardial infarction, isoprenaline, 4'ClDzp, PK-11195, L-NAME, cardiac metabolism, biochemical markers, oxidative stress, inflammatory markers, infarct field size, rat.