İsatinin izole sıçan kalbinde oluşturulan iskemi reperfüzyon hasarındaki etkileri
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Tarih
2014
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Yayıncı
Trakya Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
İsatin vücut sıvılarında bulunan, natriüretik peptid antagonisti olduğu bilinen endojen bir indoldür. Bu çalışmada isatinin izole sıçan kalbindeki hemodinamik etkisi ve isatin uygulanmasına bağlı siklik guanozin monofosfat değerlerindeki değişim incelendi. Ayrıca isatinin miyokardiyal dokuda iskemi üzerine siklooksigenaz-2 ve nükleer faktör kappa B düzeylerine etkisinin incelenmesi amaçlanmıştır. Bu çalışmada 250-350 gr ağırlığında erkek Wistar sıçanlar kullanıldı. Düşük akımlı iskeminin 30 dakika öncesinde Kontrol grubuna (n=10) serum fizyolojik, isatin grubuna (n=10) isatin (50 mg/kg) intraperitoneal olarak uygulandı. İzole kalpler Langendorf aparatına yerleştirildi. Bu gruplardaki izole kalplere 15 dakika boyunca Krebb's Henseleit solüsyonu perfüze edildi. Atriyal natriüretik peptit grubunda (n=7) ve isatin + atriyal natriüretk peptit grubunda (n=7) perfüzyon solüsyonuna atriyal natriüretik peptit (0.1 µM/L) eklendi. Tüm gruplarda sol ventrikül gelişim basıncı maksimum ve minimum basınç değişim değerleri çalışma boyunca kaydedildi. Sol ventrikül dokusunda siklooksigenaz-2 mRNA and nükleer faktör kapa B mRNA düzeyleri isatin (n=10) ve serum fizyolojik (n=10) verilmesini takiben 30 dakika sonrasında belirlendi. İsatin grubunun reperfüzyonun 60. dakikasındaki sol ventrikül gelişim basıncı değerleri (18,9 ± 17,1 mmHg) atriyal natriüretik peptit grubundan (68,9± 55,5 mmHg; p<0.05) ve isatin + atriyal natriüretik peptit grubundan (80,8± 53,2 mmHg; p<0.05) daha düşüktü. İsatin grubunda reperfüzyonun 60. dakikasında isatin ve atriyal natriüretik peptit grubuna göre azalmış minimum basınç değişimi saptandı. Atraiyal natriüretik peptit (1,22±0.07 pmol/ml) ve isatin + atriyal natriüretik peptit (1,22±0.11 pmol/ml) gruplarının perfüzyon solüsyonunda isatin grubundan (0,67±0.39 pmol/ml) daha yüksek siklik guanozin monofosfat düzeyleri saptandı(sırasıyla, p<0.01 and p<0.01). İsatin grubunda infakt alanı (19,7±7,1 %) atriyal natriüretik peptit (8,8±6,0 %; p<0.01) ve isatin + atriyal natriüretik peptit (9,1±4,2 %; p<0.01) grubundan daha fazlaydı. Grupların siklooksigenaz-2 ve nükleer faktör kapa B mRNA değerleri isatin verilmesini takiben kontrol grubuna benzer bulundu. İzole sıçan kalbinde yüksek doz isatin verilmesi kontrol grubuna benzer kontraktil etki oluşturmuş bulunmaktadır. Bununla birlikte, atriyal natriüretik peptit sıçan kalbinde reperfüzyonun 60. dakikasında siklik guanozin monofosfat düzeyini artırarak pozitif inotropik ve lusiotropik etkiler oluşturmaktadır.
Abstract
Isatin is an endogen indole which is found in the body fluids and known as natriuretic peptid reseptor blocker. The hemodynamic effects of isatin were investigated in this study. Additionally, the alterations of cyclic guanosine monophosphate levels depending on isatin in application and the effect of isatin on myocardial infact area and the effects of isatin on the levels of cyclooxygenase-2 and nükleer faktor kappa B were investigated in this study. Male Wistar rats weighted 250-350 gr were used in this study. Normal saline in control group (n=10) and isatin (50 mg/kg) in isatin group (n=10) were applied intraperitoneally to rats 30 minutes before low flow ischemia. Isolated hearts were placed in a Langendorff apparatus. Krebb's Henseleit solution perfused for 15 minutes to the isolated hearts in each group. Atriyal natriuretic peptid (0.1 µM/L) was added to the perfusion solution in atrial natriuretic peptide group (n=7) and isatin + atrial natriuretic peptide group (n=8). Left ventricular developed pressure, maximum and minimum rate of pressure development (+dp/dt and -dp/dt) were recorded during the experiments. Cyclic guanosine monophosphate levels were measured in perfusion solution before and after 30 minutes and 60-minutes of ischemia in all groups. Cyclooxygenase-2 mRNA and nuclear factor kapa B mRNA levels in left ventricle tissue were also determined 30 minute after administration of isatin (n=10) or normal saline (n=10). Left ventricular developed pressure was lower in isatin group (18,9 ± 17,1 mmHg) than atrial natriuretic peptide group (68,9± 55,5 mmHg; p<0.05) and isatin + atrial natriuretic peptide group (80,8± 53,2 mmHg; p<0.05) in reperfusion (60 minutes). Decreased dp/dtmin values were observed 60 minutes after reperfusion in isatin group than atrial natriuetic peptide group, and isatin + atrial natriuretic peptide group. Higher cyclic guanosine monophosphate values were found in reperfusion in atrial natriuretic peptide (1,22±0.07 pmol/ml) and isatin + atrial natriuretic peptide (1,22±0.11 pmol/ml) group than isatin group (0,67±0.39 pmol/ml) in perfusion solution (p<0.01 and p<0.01 respectively). Infarct size was larger in the isatin group (19,7±7,1 %) than atrial natriuretic peptide (8,8±6,0 %; p<0.01) and isatin + atrial natriuretic peptide (9,1±4,2 %; p<0.01) group. Cyclooxygenase-2 and nuclear factor kapa B mRNA values were similar with control group following isatin administrations. Similar contractil force has been observed with control values following ischemic injury after high dose of isatin administration in isolated rat heart. However, atrial natriuretic peptide may mediate positive inotropic and lusiotropic effect on the rat heart in the 60th minute of reperfusion by increasing cyclic guanosine monophosphate levels in isolated perfused rat heart.
Abstract
Isatin is an endogen indole which is found in the body fluids and known as natriuretic peptid reseptor blocker. The hemodynamic effects of isatin were investigated in this study. Additionally, the alterations of cyclic guanosine monophosphate levels depending on isatin in application and the effect of isatin on myocardial infact area and the effects of isatin on the levels of cyclooxygenase-2 and nükleer faktor kappa B were investigated in this study. Male Wistar rats weighted 250-350 gr were used in this study. Normal saline in control group (n=10) and isatin (50 mg/kg) in isatin group (n=10) were applied intraperitoneally to rats 30 minutes before low flow ischemia. Isolated hearts were placed in a Langendorff apparatus. Krebb's Henseleit solution perfused for 15 minutes to the isolated hearts in each group. Atriyal natriuretic peptid (0.1 µM/L) was added to the perfusion solution in atrial natriuretic peptide group (n=7) and isatin + atrial natriuretic peptide group (n=8). Left ventricular developed pressure, maximum and minimum rate of pressure development (+dp/dt and -dp/dt) were recorded during the experiments. Cyclic guanosine monophosphate levels were measured in perfusion solution before and after 30 minutes and 60-minutes of ischemia in all groups. Cyclooxygenase-2 mRNA and nuclear factor kapa B mRNA levels in left ventricle tissue were also determined 30 minute after administration of isatin (n=10) or normal saline (n=10). Left ventricular developed pressure was lower in isatin group (18,9 ± 17,1 mmHg) than atrial natriuretic peptide group (68,9± 55,5 mmHg; p<0.05) and isatin + atrial natriuretic peptide group (80,8± 53,2 mmHg; p<0.05) in reperfusion (60 minutes). Decreased dp/dtmin values were observed 60 minutes after reperfusion in isatin group than atrial natriuetic peptide group, and isatin + atrial natriuretic peptide group. Higher cyclic guanosine monophosphate values were found in reperfusion in atrial natriuretic peptide (1,22±0.07 pmol/ml) and isatin + atrial natriuretic peptide (1,22±0.11 pmol/ml) group than isatin group (0,67±0.39 pmol/ml) in perfusion solution (p<0.01 and p<0.01 respectively). Infarct size was larger in the isatin group (19,7±7,1 %) than atrial natriuretic peptide (8,8±6,0 %; p<0.01) and isatin + atrial natriuretic peptide (9,1±4,2 %; p<0.01) group. Cyclooxygenase-2 and nuclear factor kapa B mRNA values were similar with control group following isatin administrations. Similar contractil force has been observed with control values following ischemic injury after high dose of isatin administration in isolated rat heart. However, atrial natriuretic peptide may mediate positive inotropic and lusiotropic effect on the rat heart in the 60th minute of reperfusion by increasing cyclic guanosine monophosphate levels in isolated perfused rat heart.
Açıklama
Yüksek Lisans Tezi
Anahtar Kelimeler
Kalp, Ischemia, İsatin, Heart, Kalp Hastalıkları, Heart Diseases, Miyokardial Reperfüzyon, Myocardial Reperfusion, Miyokardial Reperfüzyon Lezyonu, Myocardial Reperfusion Injury, Natriüretik Hormon, Natriuretic Hormone, Peptidler, Peptides
