Amaç: İntraserebroventriküler (ICV) olarak enjekte edilen 'glucagon like peptid-1 (GLP-1)'in sıçanlarda gastrik mukozal kan akımı [gastric mucosal blood flow (GMBF)]'na etkisi, bu etkide santral spesifik reseptörlerinin rolü ve ayrıca absolu etanolün GMBF'de neden olduğu değişikliklerin üzerindeki etkisinin araştırılmasıdır. Gereç ve Yöntemler: ICV enjeksiyonlar için izofloran (%4) anestezisi altında sıçanların kafatasına orta hattın 1,5 mm sağ yanında ve bregmanın 1-1,5 mm arkasında olacak şekilde bir delik açıldı. Bu delikten sağ lateral ventriküle, dik olarak ve alt ucu kafatası yüzeyinden 4,2-4,5 mm kadar derinliğe inecek şekilde 10 mm uzunluğunda bir kanül yerleştirildi. GMBF 'Laser Doppler flowmetre' ile ölçülerek, veriler 'MP30 Data Acquisition System' aracılığıyla bilgisayara aktarıldı. Ölçümler için anestezi altındaki sıçanlarda mide hazırlandıktan sonra mide mukozasına prob yerleştirilerek kalibrasyon için 30 dk beklendi ve bazal kan akımı ölçümleri kaydedildi. GLP-1'in GMBF'deki etkisini araştırmak amacıyla, GLP-1 (3, 10 ve 30 μg/10 μL; ICV) veya serum fizyolojik (10 μL; ICV) enjekte edildi. Spesifik reseptör antagonisti exendin-(9-39) (1 μg/10 μL; ICV) enjekte edildikten 5 dk sonra 10 μg GLP- 1 enjekte edildi. Enjeksiyonları takiben gastrik çember içine serum fizyolojik (1,5 mL) uygulandı ve 30 dak süresince her 5 dk'da gastrik kan akımı kaydedildi. Absolu etanolün GMBF'de neden olduğu değişikler üzerinde GLP-1'in etkisini araştırmak için sıçanlara 10 μg GLP-1 enjeksiyonundan 5 dk sonra gastrik çember içine etanol (1,5 mL) uygulandı. Bulgular: 10 μg ICV GLP-1 GMBF'yi arttırdı ve ICV eksendin- (9-39) bu etkiyi antagonize etti. Ayrıca GLP-1 absolu etanolün GMBF'de oluşturduğu inhibisyonu azalttı. 3 ve 30 μg GLP-1 ise GMBF'yi azalttı. Sonuç: ICV olarak enjekte edilen 10 μg GLP-1'in GMBF'yi artırdığı ve bu etkide, santral spesifik reseptörlerinin rolü olduğu düşünülmektedir. Aynı zamanda santral GLP-1'in GMBF'deki etanol nedenli inhibisyonu önleyebildiği gözlenmiştir. Diğer dozlar ise GMBF'de azalmaya neden olmuştur.
Anahtar Kelimeler: Glukagon benzeri peptid-1; gastrik mukoza; eksendin-(9-39)
Objective: The aim of this study was to investigate the effects of intracerebroventricularly (ICV) injected glucagon like peptide-1 (GLP-1) on gastric mucosal blood flow (GMBF) in rats and the role of central-specific receptors in this effect, and the changes on GMBF induced by intragastric absolute ethanol. Material and Methods: Each animal was anaesthetized with isoflurane (4%) for ICV injections and to drill a burr hole through the skull that is 1.5 mm lateral to the midline and 1-1.5 mm posterior to bregma on the right side. Through this hole, a stainless steel hypodermic cannula of 10 mm length was placed perpendicular to the right lateral ventricle and was lowered 4.2-4.5 mm below the surface of the skull. GMBF was measured by laser Doppler flowmeter, and the data collected by computer using 'MP30 Data Acquisition' System. After preparation of the stomach for GMBF recording, a probe was placed in the gastric mucosa and basal GMBF recordings were obtained after 30-minute stabilization period. Rats were treated with GLP-1 (3, 10 and 30 μg/10 μL; ICV) or saline (10 μL; ICV) to find out the effective dose of ICV GLP-1 on GMBF. Then specific receptor antagonist exendin- (9-39) (1 μg/10 μL; ICV) was injected before the effective dose of ICV GLP-1. Subsequent to those injections serum physiologic were introduced into the gastric chamber and GMBF was recorded every fifth minute during the next 30 min. In order to confirm the effect of GLP-1 on intraluminal absolute-ethanol-induced changes in GMBF, ethanol (1.5 mL) was administrated into the gastric chamber of rats after 5 min of GLP-1 injection. Results: 10 μg ICV GLP-1 increased the GMBF and ICV exendin- (9-39) antagonized this effect. In addition, GLP-1 reduced the inhibition of absolute ethanol on GMBF. Conclusion: We suggest that, ICV GLP-1 increases GMBF and central specific receptors intermediate this effect. At the same time, it is observed that ICV GLP-1 reduced the intraluminal ethanol-induced inhibition of GMBF.
Keywords: Glucagon-like peptide 1; gastric mucosa; exendin-(9-39)
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