İnsan safen veninde yüksek glikoz ve pioglitazonun vasküler yanıtlar üzerine etkileri
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Dosyalar
Tarih
2018
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Koroner arter bypass greft (KABG) cerrahisinde greftlerin uzun dönem açık kalma oranı restenoz gelişimi nedeniyle düşüktür. Diyabet oksidatif stres oluşumuna, matriks metalloproteinazların (MMP'ler) ekspresyon/aktivitesinin artmasına yol açarak restenozu ve vasküler disfonksiyonu tetikler. Çalışmamızda insan safen ven (İSV) segmentlerinde yüksek glikozun oksidatif stress, MMP-2, MMP-9, MMP-14, TIMP-2 ekspresyonları ve vasküler fonksiyonel yanıtlar, üzerine olan etkilerinin ve pioglitazonun oluşturduğu değişimlerin araştırılması amaçlanmıştır. Gereç ve Yöntem: KABG operasyonuna alınan hastalardan sağlanan İSV segmentleri, endotelyum nazikçe uzaklaştırıldıktan sonra 5 halkaya ayrılmıştır. Halkalara 30mM glikoz ve/veya 10µM pioglitazon veya 0.1% DMSO eklenmiş DMEM/F12 ortamında 24 saat inkübasyon uygulanmıştır. İşlem görmemiş halkalar kontrol olarak adlandırılmıştır. Süperoksit anyon/ ROT düzeyleri lusigenin/luminol kemilüminesans yöntemi ile, MMP-2, MMP-9 ekspresyon/aktiviteleri jelatin zimografi ile, MMP-14 ve TIMP-2 ekspresyonları ise immünohistokimyasal olarak incelenmiştir.İSV halkalarında izole organ banyosu sistemi kullanılarakpotasyum klorür, noradrenalin, serotonin ve prostaglandin F2α'ya karşı kasılma ve diltiazem ile papaverine karşı gevşeme yanıtları alınmıştır. Bulgular: Yüksek glikoz süperoksit anyon ve ROT düzeylerini artırmış, ancak pioglitazon artan düzeyleri azaltmıştır. Glikoz MMP-2, MMP-14 ekspresyonlarını, MMP-2 aktivitesini artırmış, TIMP-2 ekspresyonunu ise azaltmıştır. Pioglitazon MMP-2, MMP-14 ekspresyonlarını ve MMP-2 aktivitesini inhibe etmiş, ancak TIMP-2'yi artırmıştır. Glikoz İSV segmentlerinde potasyum klorür, noradrenalin, serotonin, prostaglandin F2α'ya karşı kontraktil yanıtları anlamlı şekilde azaltmıştır. Pioglitazon tüm ajanlara karşı kontraktil yanıtları artırmıştır. Glikoz diltiazeme karşı gevşeme yanıtlarını azaltmış, ancak pioglitazon etkilememiştir. Papaverin yanıtları glikoz veya pioglitazondan etkilenmemiştir. Glikoz kontraktil ajanlara karşı duyarlılığı azaltmış, pioglitazon serotonin ve prostaglandinF2α'ya karşı duyarlılığı artırmış, noradrenaline karşı duyarlılığı etkilememiştir. Sonuç: Pioglitazon tedavisi İSV grefti uygulanan diyabet hastalarında restenoza bağlı erken greft yetmezliğinin önlenmesi ve greftin fonksiyonel performansının uzun süre korunması için yararlı olabilir.
Objective: The long-term patency rate of grafts in coronary artery bypass grafting (CABG) surgery is low due to restenosis. Diabetes induces restenosis and vascular dysfunction leading to increased expression/activity of matrix metalloproteinases (MMPs) and oxidative stress formation. In our study, it was aimed to investigate the effects of high glucose on oxidative stress, expressions of MMP-2, MMP-9, MMP-14, TIMP-2 and vascular functional responses,and changes with pioglitazone in human saphenous vein (HSV) segments. Materials and Methods: HSV segments obtained from patients undergoing CABG were separated into 5 rings after the endothelium was gently removed. The rings were incubated in DMEM/F12 medium supplemented with 30mM glucose and/or 10mM pioglitazone or 0.1% DMSO for 24hrs. Untreated rings were called as controls. The levels of superoxide anion/reactive oxygen species (ROS) were examined by lucigenin/luminol chemiluminescence assay. MMP-2, MMP-9 expressions/activitieswere determined by gelatin zymography and MMP-14, TIMP-2 expressions were studied by immunohistochemistry. In the HSV rings, contractile responses to potassium chloride, noradrenaline, serotonin and prostaglandin F2α and relaxation responses to diltiazem and papaverine were performedby using an isolated organ bath system. Results: High glucose increased superoxide anion and ROS levels, but pioglitazone decreased the levels. Glucose increased MMP-2, MMP-14 expressions, MMP-2 activity, and decreased TIMP-2 expression. Pioglitazone inhibited MMP-2, MMP-14 expressions and MMP-2 activity, but increased TIMP-2.Glucose reduced responses to all contractile agents used but pioglitazone increased the responses in the HSV segments. Glucose reduced relaxation responses to diltiazem, but pioglitazone did not affect them. Papaverine responses were not affected by glucose or pioglitazone. Glucose decreased sensitivity to contractile agents, pioglitazone increased susceptibility to serotonin and prostaglandin F2α, but not to noradrenaline. Conclusion:Pioglitazone treatment may be useful for preventing early graft failure due to restenosis and for prolonged preservation of the functional performance of the graftin diabetic patients who have received HSV graft.
Objective: The long-term patency rate of grafts in coronary artery bypass grafting (CABG) surgery is low due to restenosis. Diabetes induces restenosis and vascular dysfunction leading to increased expression/activity of matrix metalloproteinases (MMPs) and oxidative stress formation. In our study, it was aimed to investigate the effects of high glucose on oxidative stress, expressions of MMP-2, MMP-9, MMP-14, TIMP-2 and vascular functional responses,and changes with pioglitazone in human saphenous vein (HSV) segments. Materials and Methods: HSV segments obtained from patients undergoing CABG were separated into 5 rings after the endothelium was gently removed. The rings were incubated in DMEM/F12 medium supplemented with 30mM glucose and/or 10mM pioglitazone or 0.1% DMSO for 24hrs. Untreated rings were called as controls. The levels of superoxide anion/reactive oxygen species (ROS) were examined by lucigenin/luminol chemiluminescence assay. MMP-2, MMP-9 expressions/activitieswere determined by gelatin zymography and MMP-14, TIMP-2 expressions were studied by immunohistochemistry. In the HSV rings, contractile responses to potassium chloride, noradrenaline, serotonin and prostaglandin F2α and relaxation responses to diltiazem and papaverine were performedby using an isolated organ bath system. Results: High glucose increased superoxide anion and ROS levels, but pioglitazone decreased the levels. Glucose increased MMP-2, MMP-14 expressions, MMP-2 activity, and decreased TIMP-2 expression. Pioglitazone inhibited MMP-2, MMP-14 expressions and MMP-2 activity, but increased TIMP-2.Glucose reduced responses to all contractile agents used but pioglitazone increased the responses in the HSV segments. Glucose reduced relaxation responses to diltiazem, but pioglitazone did not affect them. Papaverine responses were not affected by glucose or pioglitazone. Glucose decreased sensitivity to contractile agents, pioglitazone increased susceptibility to serotonin and prostaglandin F2α, but not to noradrenaline. Conclusion:Pioglitazone treatment may be useful for preventing early graft failure due to restenosis and for prolonged preservation of the functional performance of the graftin diabetic patients who have received HSV graft.
Açıklama
Anahtar Kelimeler
Pioglitazon, Yüksek Glikoz, Matriks Metalloproteinazlar, Oksidatif Stres, Koroner Arter Bypass Grefti, Pioglitazone, High Glucose, Matrix Metalloproteinases, Oxidative Stress, Corronary Artery Bypass Graft
