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Yeni Doğan Streptozotosin Diyabetik Nefropatide İsradipin’in TGF-ß1 ve Tip IV Kollajen Ekspresyonları Üzerine Etkileri

The effects of isradipine on TGF-ß1 and type IV collagen expression in neonatal streptozotocin diabetic nephropathy

Journal Name:

  • Cerrahpaşa Tıp Dergisi

Publication Year:

  • 2007

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Abstract (2. Language): 
The effects of isradipine on TGF-ß1 and type IV collagen expression in neonatal STZ diabetic nephropathy In this study, the effects of isradipine as a calcium channel blocker, on glomerulus structural alterations and renal functions were examined in the neonatal streptozotocin diabetes (n-STZ) model. We used 4 groups of newborn Wistar rats. On the 2nd day of birth after STZ (100 mg/kg) injection to the 1st and 2nd group, isradipine (5 mg/kg, i.p) was administered to the 2nd group for 6 weeks from 12 weeks on. The 3rd group was isradipine treated (5 mg/kg, i.p., from 6 weeks to 12 weeks) control group and the 4th group was healty control. During the period of the experiment, blood glucose levels, body weight and microalbuminuria level of the rats were measured. Kidneys were weighted. Tissue sections were immunostained using monoclonal type IV collagen and TGF-ß1 antibodies. The blood glucose levels were markedly decreased in the isradipine treated cortrols. Microalbuminuria levels were decreased in treated diabetics compared to diabetic group. Kidney weights were increased in n-STZ diabetics when compared to non-diabetics. Glomeruli dimensions of n-STZ diabetics were increased in comparison to nondiabetic control group. In the isradipine treated diabetic group the larger glomeruli were observed according to the nondiabetic group. Basal membrane thickening in glomerulus and significant increase in mesangial matrix and mesangial cells and an increased type IV collagen and TGF-ß1 expression in n-STZ diabetics were observed. In the isradipine treated groups type IV collagen and TGF-ß1 immunoreactivity in glomerulus were seen to be similar to nondiabetic controls. Our results show that isradipine could be effective in delaying the progression of nephropathy by decreasing microalbuminuria and blood glucose levels but it didnot completly improved renal morphology.
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Abstract (Original Language): 
Bu çalışmada; kalsiyum kanal blokeri olan isradipin’in Tip II diyabetine uygunluk gösteren yeni doğan sıçan streptozotosin (YD-STZ) diyabet modelinde renal fonksiyonlar ve glomerulun yapısal değişimleri üzerine etkilerini incelendi. Yeni doğan wistar türü albino sıçanlardan 4 grup oluşturuldu. 1. ve 2.gruba; doğumu izleyen 2.günde STZ (100 mg/kg, i.p, tek doz) uygulandı. 1.grup;YD-STZ diyabetik kontrol grubu olarak ayrıldı. 2.gruba; 12.haftadan itibaren İsradipin (5 mg/kg/gün, 6 hafta, i.p.) uygulandı. 3.grup; diyabetik olmayan sağlıklı sıçanlara 12. haftadan itibaren isradipin (5 mg/kg/gün, 6 hafta) uygulandı. 4.grup; sağlıklı kontrol grubu olarak ayrıldı. Çalışma süresince tüm gruplardaki hayvanların kan glukoz düzeyi ölçümleri, vucut ağırlık ölçümleri ve mikro-albüminüri düzey ölçümleri yapıdı. Böbrek doku kesitlerine Periodik Asit Schiff boyaması ve TGF-β1, tip IV kollajen antikoru ile immünohistokimyasal boyamalar yapıldı. İsradipin uygulanan diyabetik grubun kan glukoz düzeylerinde belirgin düşme saptandı. Diyabetik gruba kıyasla tedavili diyabetiklerde mikro-albüminüri düzeylerinde anlamlı azalma saptandı. Böbrek ağırlıkları; diyabetik grupta, sağlıklı kontrol gruba kıyasla artış gösterirken, tedavili diyabetik grupta azalma saptandı. Tedavisiz diyabetik grubun diğer gruplardan daha büyük boyutta glomeruller içerdikleri saptandı. Diyabetiklerde glomerul ve tubullerde bazal membran kalınlaşması, belirgin mezangiyal matriks ve hücre artışı gözlendi. YD-STZ diyabetiklerde glomerul membran kalınlaşması, TGF-β1 ve tip IV kollajen immünreaktivitesinde artış gözlendi. İsradipin uygulanan diyabetik gruptaki TGF-β1 ve tip IV kollajen immunreaktivitesi sağlıklı kontrol grubuna benzerdi. İsradipin’in kullanılan doz ve sürede, bu diyabet modelinde renal doku hasarını önlemede yetersiz olduğu, ancak kan glukoz ve mikro-albüminüri düzeylerinin azaltarak diyabetik nefropatinin ilerlemesini yavaşlattığı sonucuna varıldı.
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