Publication: Nöropeptit W (NPW)’nin sıçanlarda mide fonksiyonları üzerine etkilerinin araştırılması
Abstract
Amaç: Nöropeptit W (NPW), hipotalamus-hipofiz-adrenal bez ekseninin (HPA) aktivasyonuna ve nöroendokrin fonksiyonların merkezi düzenlenmesine katkıda bulunur. Çalışmamızda periferik verilen NPW’nin stresle indüklenen mide ülserinde gelişen oksidan hasara olan etkilerini ve bu etkilerinde HPA’nın, mide motor aktivitesindeki değişikliklerin ve vagovagal kolinerjik yolun katkılarını ortaya koymak hedeflenmiştir.Gereç ve yöntem: Stres ülseri modeli (WIRS), mide boşalma hızı ölçümü ve mide düz kası kasılması şeklindeki üç ayrı deney protokolünde Sprague Dawley erkek sıçanlar (n=131) kullanıldı. WIRS’den hemen önce sıçanlara serum fizyolojik (SF) veya NPW (0,1; 0,3; 1 veya 5 μg/ kg) cilt altından uygulandı. Vagal afferent denervasyonlu (VAD) gruplarda perivagal kapsaisin uygulamasından 2 hafta sonra WIRS gerçekleştirildi. WIRS’i takiben serozal kan akımı ölçüldü. Midede oksidan hasar ve inflamasyon parametreleri ile beyin/ mide NPW mRNA düzeyleri belirlendi ve histopatolojik değerlendirmeler yapıldı.Bulgular: NPW ön-tedavisi midede WIRS’le gelişen oksidan hasarı hafifletti, kan akımını artırdı, serum IL-6 ve TNF-α düzeylerindeki artışı engelledi ve sikloksijenaz-1 mRNA seviyesini artırıp sikloksijenaz-2 mRNA’sını baskıladı; ancak stresle artan HPA aktivitesini değiştirmedi. Düşük doz NPW’nin malondialdehit ve miyeloperoksidaz aktivitesi düzeylerini baskılayıcı ve kan akımını artırıcı etkileri VAD’li gruplarda ortadan kalktı. Ülserde baskılanan beyin NPW mRNA ekspresyonunu yüksek doz NPW ile arttı. Sıvıların mideden boşalma hızları NPW ile baskılanırken antrum düz kasındaki kasılma yanıtı NPW ile azaldı ve bu etkilerde kolesistokinin-1 ve kolesistokinin-2 reseptörlerinin aracı olduğu gözlendi.Sonuç: Periferik uygulanan NPW’nin mide kan akımını artırıp, oksidan hasarı, inflamasyonu ve mide motor aktivitesini baskılayarak stres ülseri modelinde gastroprotektif etki gösterdiği ortaya kondu. NPW’nin bu etkilerinin HPA aktivitesinden bağımsız olduğu, ama vagal afferent sinirlerin katılımıyla gerçekleştiği belirlendi.
Objectives: Neuropeptide W (NPW) contributes to hypothalamic-pituitary-adrenal gland axis (HPA) activity and central regulation of neuroendocrine functions. The aim was to investigate effects of NPW on stress-induced gastric ulcers and contribution of HPA, gastric motor activity and vagovagal cholinergic pathway in these effects.Methods: Sprague Dawley male rats (n=131) were used in three experimental procedures: stress ulcer model (WIRS), gastric emptying rate measurement and gastric smooth muscle contraction. Saline or NPW (0.1; 0.3; 1 or 5 μg/ kg) was injected subcutaneously before WIRS induction. Capsaicin was applied perivagally to degenerate vagal afferent fibers (VAD) and two weeks later WIRS was induced. Following WIRS, serosal blood flow was measured, and gastric tissues were removed for measuring oxidative damage and inflammation indicators, evaluating histopathologically and determining brain/ stomach NPW mRNA levels.Results: NPW pre-treatment alleviated WIRS-induced gastric oxidant damage, increased blood flow, prevented elevations in serum IL-6 and TNF-α levels, and increased cycloxygenase-1 mRNA, but suppressed cycloxygenase-2 mRNA levels. Stress-induced HPA hyperactivity was not altered by NPW. Inhibitory effect of low-dose NPW on malondialdehyde and myeloperoxidase activity and its stimulatory effect on blood flow were abolished by VAD. Suppressed brain NPW mRNA expression with ulcer induction was upregulated by high-dose NPW. NPW suppressed gastric emptying rate and antrum muscle contractility via the contribution of cholecystokinin-1 and cholecystokinin-2 receptors.Conclusion: Peripherally administered NPW exerts a gastroprotective effect by increasing gastric blood flow and suppressing oxidative damage, inflammation and gastric motor activity. These effects are mediated by vagal afferent nerves, but are independent of HPA activity.
Objectives: Neuropeptide W (NPW) contributes to hypothalamic-pituitary-adrenal gland axis (HPA) activity and central regulation of neuroendocrine functions. The aim was to investigate effects of NPW on stress-induced gastric ulcers and contribution of HPA, gastric motor activity and vagovagal cholinergic pathway in these effects.Methods: Sprague Dawley male rats (n=131) were used in three experimental procedures: stress ulcer model (WIRS), gastric emptying rate measurement and gastric smooth muscle contraction. Saline or NPW (0.1; 0.3; 1 or 5 μg/ kg) was injected subcutaneously before WIRS induction. Capsaicin was applied perivagally to degenerate vagal afferent fibers (VAD) and two weeks later WIRS was induced. Following WIRS, serosal blood flow was measured, and gastric tissues were removed for measuring oxidative damage and inflammation indicators, evaluating histopathologically and determining brain/ stomach NPW mRNA levels.Results: NPW pre-treatment alleviated WIRS-induced gastric oxidant damage, increased blood flow, prevented elevations in serum IL-6 and TNF-α levels, and increased cycloxygenase-1 mRNA, but suppressed cycloxygenase-2 mRNA levels. Stress-induced HPA hyperactivity was not altered by NPW. Inhibitory effect of low-dose NPW on malondialdehyde and myeloperoxidase activity and its stimulatory effect on blood flow were abolished by VAD. Suppressed brain NPW mRNA expression with ulcer induction was upregulated by high-dose NPW. NPW suppressed gastric emptying rate and antrum muscle contractility via the contribution of cholecystokinin-1 and cholecystokinin-2 receptors.Conclusion: Peripherally administered NPW exerts a gastroprotective effect by increasing gastric blood flow and suppressing oxidative damage, inflammation and gastric motor activity. These effects are mediated by vagal afferent nerves, but are independent of HPA activity.