Gestasyonel diyabetli ve normal gebelerden izole edilen umbilikal arterlerde Anjiyotensin II ve TLR4 ilişkisinin incelenmesi
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Tarih
2021
Yazarlar
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Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Bu in vitro çalışmada, normal ve gestasyonel diyabetes mellitus (GDM) olan gebelerden alınan umbilikal arterlerde Anjiotensin II (AII) ile Toll Benzeri Reseptör 4 (TLR4) ilişkisi araştırılmıştır. Normal ve GDM'li arterlerde AII'nin vazokonstriktör etkileri, bu etkilerin TLR4 agonist ve antagonistleriyle değişimi; ayrıca, normal ve GDM umbilikal arterlerinde AII ve TLR4 mRNA ekspresyonları belirlenmiştir. Normal ve GDM'li umbilikal kordlardan hazırlanan arter preparatları 37°C' de sabit tutulan ve %95 O2-%5 CO2 karışımı ile sürekli gazlandırılan Krebs-Henseleit solüsyonu (KHS) içeren izole organ banyolarına alınmış ve uygulanan ajanlara alınan cevaplar izometrik olarak kaydedilmiştir. Normal ve GDM umbilikal arterlerde AII'nin (10-9-10-4 M) maksimum kasılma cevapları arasında anlamlı bir fark olmadığı; pD2 değerleri karşılaştırıldığında ise, GDM grubunda AII'ye duyarlılık artışı olduğu saptanmıştır. GDM grubu umbilikal arterlerde Nω-Nitro-L-Arjinin Metil Ester Hidroklorür (L-NAME) (10-4 M, 20 dakika (dk.)) ve lipopolisakkarit (LPS) (0,3 μg/ml, 90 dk.) ile inkübasyon normal gebelerden alınan umbilikal arterlerden farklı olarak AII'ye duyarlılık artışı oluşmamıştır. Dokuların TAK-242 (10-6 M, 20 dk.) ile inkübasyonu GDM'li arterlerde normal gruptan farklı olarak maksimum cevabı değiştirmemiş fakat, AII'ye duyarlılığı azaltmıştır. BBR (10-5 M, 30 dk.) ise, GDM grubunda normal dokulardan farklı olarak maksimum cevap ve duyarlılıkta değişme oluşturmamıştır. RT-PCR analizinde ise, normal ve GDM umbilikal arterlerde TLR4 ve Anjiyotensin II tip 1 reseptör (AT1) geni AGTR1'in mRNA düzeyinde ekspresyonları ölçülmüştür. Yapılan ölçümlerde gruplar arasında anlamlı bir farka rastlanmamıştır. Bu sonuçlar, normal ve GDM umbilikal arterleri arasında AII'nin vazokonstriktör etkisinin TLR4 reseptörü aracılığıyla kısmen modüle edilebileceğini göstermektedir. Bu çalışma, AII ve TLR4'ü ilişkilendiren literatür bulgularıyla paralellik göstermektedir. Ancak, örnek sayısı artırılarak yapılacak daha kapsamlı çalışmalara ihtiyaç vardır.
It has been investigated the relationship of Angiotensin II and Toll Like Receptor 4 (TLR4) in umbilical arteries of pregnants with normal and gestational diabetes mellitus (GDM) in this study in vitro. Vasoconstrictor effects of AII, the changes of these effects with the TLR4 agonist and antagonists, and mRNA expression levels of normal and GDM umbilical arteries have been determined. Prepared arteries from normal and GDM umbilical cords have been inserted in an isolated organ bath filled with Krebs-Henseleit solution (KHS) and aired with a mixture of 95% O2 -5% CO2 under fixed temperature at 37°C and responses after agent applications have been recorded isometrically. No statistical significance has been observed in maximum contraction responses of AII (10-9-10-4 M) in normal and GDM umbilical arteries. As for the comparison of pD2 values, increased sensitivity to AII has been shown in the GDM group. There is no increased sensitivity to AII has been seen in the GDM group umbilical arteries with the incubation of Nω -Nitro-L-arginine methyl ester hydrochloride (L-NAME) (10-4 M, 20 minutes (min.)) and lipopolysaccharide (LPS) (0.3 μg/ml, 90 min.) contrary to normal arteries. As distinct from the normal group, the tissue incubation with TAK-242 (10-6 M, 20 min.) has not changed the maximum contraction response in the GDM arteries. However, sensitivity to AII has been reduced. No difference has been determined in the maximum contraction response and the sensitivity after BBR (10-5 M, 30 min.) incubation dissimilar from the normal tissues. mRNA expression levels of TLR4 and Angiotensin II type 1 receptor (AT1) gene AGTR1 have been measured. No statistical difference has been noted between the measured groups in the RT-PCR analysis. As a consequence, it has been shown TLR4 partially modulates vasoconstrictive effect of AII between the normal and GDM umbilical arteries. This study is in comply with literature findings on the affiliation of AII and TLR4. However, more comprehensive studies with high subject numbers are needed.
It has been investigated the relationship of Angiotensin II and Toll Like Receptor 4 (TLR4) in umbilical arteries of pregnants with normal and gestational diabetes mellitus (GDM) in this study in vitro. Vasoconstrictor effects of AII, the changes of these effects with the TLR4 agonist and antagonists, and mRNA expression levels of normal and GDM umbilical arteries have been determined. Prepared arteries from normal and GDM umbilical cords have been inserted in an isolated organ bath filled with Krebs-Henseleit solution (KHS) and aired with a mixture of 95% O2 -5% CO2 under fixed temperature at 37°C and responses after agent applications have been recorded isometrically. No statistical significance has been observed in maximum contraction responses of AII (10-9-10-4 M) in normal and GDM umbilical arteries. As for the comparison of pD2 values, increased sensitivity to AII has been shown in the GDM group. There is no increased sensitivity to AII has been seen in the GDM group umbilical arteries with the incubation of Nω -Nitro-L-arginine methyl ester hydrochloride (L-NAME) (10-4 M, 20 minutes (min.)) and lipopolysaccharide (LPS) (0.3 μg/ml, 90 min.) contrary to normal arteries. As distinct from the normal group, the tissue incubation with TAK-242 (10-6 M, 20 min.) has not changed the maximum contraction response in the GDM arteries. However, sensitivity to AII has been reduced. No difference has been determined in the maximum contraction response and the sensitivity after BBR (10-5 M, 30 min.) incubation dissimilar from the normal tissues. mRNA expression levels of TLR4 and Angiotensin II type 1 receptor (AT1) gene AGTR1 have been measured. No statistical difference has been noted between the measured groups in the RT-PCR analysis. As a consequence, it has been shown TLR4 partially modulates vasoconstrictive effect of AII between the normal and GDM umbilical arteries. This study is in comply with literature findings on the affiliation of AII and TLR4. However, more comprehensive studies with high subject numbers are needed.
Açıklama
Doktora Tezi
Anahtar Kelimeler
Anjiyotensin II, Gestasyonel Diyabetes Mellitus, LPS, TAK-242, TLR4, Angiotensin II, Gestational Diabetes Mellitus
Kaynak
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Künye
Büyük, E. (2021). Gestasyonel diyabetli ve normal gebelerden izole edilen umbilikal arterlerde Anjiyotensin II ve TLR4 ilişkisinin incelenmesi. (Yayımlanmamış doktora tezi). Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü, Tıbbi Farmakoloji Anabilim Dalı, Konya.
