Deneysel Hipertansiyon Oluşturulan Sıçanlarda Rosuvastatinin Böbrek Üzerine Koruyucu Etkileri

Abstract

Amaç: Hipertansiyon, son dönem böbrek hastalığına ulaşan hastaların yaklaşık %30'undan sorumludur. Statin tedavisinin böbrek hastalığı gelişme riskini azalttığı bilinmektedir. Bu çalışmada, L-arginin analoğu N-Nitro-L-Arjinin Metil Ester (L-NAME) kullanılarak hipertansiyon oluşturulmuş sıçanların böbrek dokusunda kaspaz-3 ve fibrillin1 (FBN1) üzerindeki değişikliklere bakılarak, hipertansiyonun bu moleküller üzerinde oluşturduğu değişiklikleri rosuvastatinin ne şekilde etkilediği araştırıldı. Araçlar ve Yöntem: Çalışmada, 200-220 g ağırlığında 18 adet Wistar Albino erkek sıçan kullanıldı. Sıçanlar her grupta 6 hayvan olacak şekilde 3 gruba ayrıldı (1.Kontrol, 2.Hipertansiyon, 3.Rosuvatatin). Hipertansiyon oluşturmak için sıçanlara 7 hafta boyunca nitrik oksit sentaz (NOS) inhibitörü L-NAME içme suyuna karıştırılarak verildi. İkinci hafta sonrasında rosuvastatin (10 mg/kg/gün) 5 hafta boyunca oral gavaj ile verildi. Kan basıncı değerleri 0, 14, 28 ve 42. günlerde tail-cuff yöntemi kullanılarak değerlendirildi. Deney bitiminde tüm sıçanlar dekapite edilerek böbrek dokularında kaspaz-3 ve FBN1 düzeyleri immunohistokimyasal yöntemle değerlendirildi. Bulgular: Kan basınçları hipertansiyon grubunda kontrolle kıyaslandığında 14, 28, 42. günlerde anlamlı düzeyde yüksek bulundu (p=0.001). Rosuvastatin 28. ve 42. günde anlamlı olmayan bir azalmaya sebep oldu. Kontrol grubuyla kıyaslandığında hipertansiyon grubunda kaspaz-3 (p=0.001) ve FBN1 (p=0.001) immünreaktivitesinin istatistiksel düzeyde anlamlı bir seviyede arttığı görüldü. Hipertansiyon grubu ile kıyaslandığında rosuvastatin verilen grupta ise, kaspaz-3 (p=0.031) ve FBN1 (p=0.030) immünreaktivitesi anlamlı azaldı. Ancak, kontrol grubuna göre rosuvastatin grubunda kaspaz-3 (p=0.036) ve FBN1 (p=0.041) immünreaktivitesinin arttığı izlendi. Sonuç: Rosuvastatin kan basınçlarını anlamlı olarak düşürmese de, hipertansif böbrekler üzerine koruyucu etkisinde kaspaz-3 ve FBN1’in aracı olabileceği düşünülmektedir.

Keywords

• Statin
• Kaspaz-3
• Fibrilin-1
• L-NAME

Protective Effects of Rosuvastatin on Kidney in Experimental Hypertension Rats Models

Abstract

Purpose: Hypertension is responsible for approximately 30% of patients who reach end-stage renal disease. Statin is known to reduce the risk of developing kidney disease. In this study, the changes in caspase-3 and fibrillin1 in the kidney tissue of rats with hypertension using L-NAME were investigated along with how rosuvastatin affected the changes caused by hypertension on these proteins. Materials and Methods: 18 Wistar Albino male rats weighing 200-220 g were used in the study. The rats were divided into 3 groups with 6 animals in each group (1.Control, 2.Hypertension, 3.Rosuvastatin).To induce hypertension, rats were given L-NAME for 7 weeks. After the second week, rosuvastatin was given by oral gavage for 5 weeks. Blood pressure values were evaluated on days 0, 14, 28, 42. At the end of the experiment, all rats were sacrificed and caspase-3 and fibrillin1 levels were evaluated. Results: Blood pressures were found to be higher in the hypertension group on the 14th, 28th, and 42nd days (p=0.001). Rosuvastatin caused a decrease that was found to be insignificant at 28th, 42nd days. Caspase-3 (p=0.001), fibrillin1 (p=0.001) immunoreactivity were found to be increased in the hypertension group. Compared with the hypertension group, caspase-3 (p=0.031), fibrillin1 (p=0.030) immunoreactivity were decreased in the rosuvastatin group. However, caspase-3 (p=0.036) and fibrillin1 (p=0.041) immunoreactivity was increased in the rosuvastatin group compared to the control group. Conclusion: Although rosuvastatin didn’t significantly decrease blood pressure, it is thought that caspase-3 and fibrillin1 may mediate its protective effect on hypertensive kidneys.

Keywords

• L-NAME
• statin
• caspase-3
• fibrillin-1

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