Obez Sıçanların Böbrek Dokularında N-Asetilsistein Kullanımının Endoplazmik Retikulum Stresi Üzerine Etkisi

Endoplazmik retikulum (ER) stresi son zamanlarda obezite ile ilişkili böbrek hastalığının patogenezinde artan bir önem kazanmıştır. N-asetilsistein (NAC), hücrelerde antioksidan üretimini artırarak doğrudan ve dolaylı olarak çalışan bir antioksidandır. Çalışmada, kalorinin %60’ını yağdan elde eden bir diyet ile obezite modeli oluşturuldu. NAC ve obezite + NAC (ObNAC) gruplarında NAC intragastrik tüp ile 150 mg/kg dozunda sekiz hafta süreyle uygulandı. Deney sonunda elde edilen böbrek dokularından alınan kesitlerde GRP78 ve PERK ekspresyonları immünohistokimyasal olarak belirlendi. GRP78'in H skoru obez grubunda kontrol, NAC ve ObNAC gruplarına göre anlamlı olarak yüksekti (p<0.01). ObNAC grubundaki H skoru, obez grubundan önemli ölçüde düşüktü (p < 0.01). Ayrıca bu grubun skoru kontrol ve NAC gruplarıyla benzerdi. Obez grubunda PERK H skoru kontrol, NAC ve ObNAC gruplarına göre anlamlı olarak yüksekti (p<0.01). ObNAC grubunda H skoru obez grubuna göre anlamlı olarak düşük (p<0.01), kontrol ve NAC gruplarına göre anlamlı olarak yüksekti (p<0.01). Yüksek yağlı diyet ile oluşan obezite böbrek dokusunda ER stresine neden olduğundan stres belirteçlerinde artan değişikliklerin NAC uygulaması ile iyileştirilebileceği düşünülebilir.

Anahtar Kelimeler:

ER stres, GRP78, N-asetilsistein, Obezite, PERK

The Effect of N-Acetylcysteine Use on Endoplasmic Reticulum Stress in the Kidney Tissues of Obese Rats

Endoplasmic reticulum (ER) stress has recently acquired increasing importance in the pathogenesis of obesity-associated kidney disease. N-acetylcysteine, otherwise known as NAC, is an antioxidant that works directly and indirectly by increasing the production of antioxidants in cells. A diet consisting of 60% calories from fat was used to establish the obesity model for the present investigation. In the NAC and obesity + NAC (ObNAC) groups, NAC was administered by intragastric tube at 150 mg/kg for eight weeks. GRP78 and PERK expressions were determined immunohistochemically in sections collected from kidney tissues at the end of the experiment. The GRP78 H score was significantly higher in the obese group than in the control, NAC, and ObNAC groups (p<0.01). The ObNAC group H-score was significantly lower than that of the obese group (p < 0.01) but was not different from the control and NAC groups. The obese group PERK H-score was also significantly higher than the control, NAC, and ObNAC groups (p<0.01). In the ObNAC group, the H-score was significantly lower than that in the obese group (p<0.01) and significantly higher than those in the control and NAC groups (p<0.01). Increasing changes in stress markers may be improved by NAC application, since obesity induced by a high-fat diet activates ER stress in kidney tissue.

Keywords:

ER stress, GRP78, N-acetylcysteine, Obesity, PERK,

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