Özlem GÜLER, Mustafa YILDIZ, Mehmet Nuri BOZDEMİR, Ahmet KAVAKLI, Adile Ferda DAĞLI, Bilal ÜSTÜNDAĞ

Deneysel Beyin İskemisinde Tacrolimusun Endotelin-1, Melatonin ve Heat Shock Protein-70 Üzerine Etkileri

Amaç: Bu çalışmada deneysel iskemik inmede tacrolimusun plazma endotelin-1, melatonin ve beyin Hsp-70 seviyeleri üzerine etkilerini araştırmayı amaçladık. Gereç ve Yöntem: Yirmi bir erkek Wistar-Albino rat her birinde yedi rat olan 3 grupa rasgele ayrıldı. Grup 2 ve grup 3'deki hayvanların ana karotis arterleri anestezi altında 10 dakika süresince anevrizma klempleri ile bağlandı. Grup 1'deki hayvanlar bağlanmadı ve herhangi bir tedavi almadı. Grup 2'deki ratlara 1 ml salin ve grup 3'dekilere 1 mg/kg tacrolimus intraperitonal olarak verildi. Enjeksiyonlar iskemiden 1 saat önce ve iskemiden 6,24 ve 48 ve 72 saat sonra uygulandı. Tüm hayvanların 4. günde kafaları kesildi, plazmaları ve beyinleri alındı. Plazma endotelin-1 ve melatonin seviyeleri ölçüldü. Beyin Hsp-70 immünboyanması ve nöron hücre ölümü yarı nicel olarak ölçüldü.Bulgular: Plazma endotelin-1 seviyeleri grup 3'de grup 2'den daha yüksekti, ancak grup 1 ve grup 2'de benzerdi. Grup 1 deki plazma melatonin seviyeleri grup 2 ve grup 3'den daha düşüktü. Grup 2'deki melatonin seviyeleri grup 3'den daha yüksekti. Grup 3'deki hücre ölümü grup 2'den daha düşüktü. Grup 2'deki ortalama Hsp-70 immün boyanma yoğunluğu grup 3 ve grup 1'den daha fazlaydı. Grup 1'deki ortalama Hsp-70 immün boyanma yoğunluğu grup 3'den daha düşüktü. Sonuç: İskemik inmede tacrolimus uygulanması plazma melatonin ve beyin Hsp-70 seviyelerini azaltır, plazma endotelin-1 seviyelerini arttırır ve nöroprotektif etki gösterir.

Anahtar Kelimeler:

ischemic stroke, melatonin, tacrolimus, Endothelin-1, Heat Shock Protein-70, tacrolimus

Effects of Tacrolimus on Endothelin-1, Melatonin and Heat Shock Protein Levels in Experimental Brain Ischemia

Objective: We aimed to investigate the effects of tacrolimus on plasma endothelin-1, melatonin and brain Hsp-70 levels in experimental ischemic stroke in this study.Material and Methods: Twenty-one male Wistar-Albino rats randomly divided into three groups which included seven rats. Animals in group 2 and group 3 were anesthetized and bilateral common carotid arteries were clamped with aneurysm clips for 10 minutes. Animals in group 1 were not clamped and were not given any treatment. Rats in group 2 were received 1 ml saline and in group 3 were received 1 mg/kg tacrolimus intraperitoneally. Injections were applied 1st hour before ischemia and at 6th, 24th, 48th and 72nd hours post ischemia. All the animals were decapitated on the 4th day and plasmas were obtained and brains were excised. Plasma endothelin-1 and melatonin levels were measured. Brain Hsp-70 immunostaining and neuron cell death were scored semiquantitatively.Results: The plasma endothelin-1 levels in group 3 were higher than group 2 and group 1, but were similar in group 1 and group 2. In group 1 plasma melatonin levels were lesser than group 2 and group 3. In group 2 plasma melatonin levels were higher than group 3. The mean neuron death in group 3 was lesser than in group 2. The mean Hsp-70 immunostaining intensity in group 2 was greater than group 3 and group 1. In group 1 the mean Hsp-70 immünostaining intensity was lesser than group 3. Conclusions: Tacrolimus administration in ischemic stroke reduces plasma melatonin and brain Hsp-70 levels and increases plasma endothelin-1 levels and has neuroprotective effect.

Keywords:

Endothelin-1, Heat Shock Protein-70, ischemic stroke, melatonin, tacrolimus,

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