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DÎABETÎK RAT MODELİNDE KISA SÜRELÎ DÜŞÜK MOLEKÜL AĞIRLIKLI HEPARIN TEDAVİSİNİN RENAL ETKÎLERÎ

RENAL EFFECTS OF SHORT TERM LOW MOLECULAR WEIGHT HEPARIN ADMINISTRATION IN DIABETIC RAT MODEL

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Abstract (2. Language): 
Abnormal glycosaminoglycan metabolism is invol¬ved in the pathogenesis of diabetic nephropathy. Glo-merular membrane anionic charge depletion leading to albuminuria is associated with loss of glycosami-noglycan in urine. It's well known that long term ad¬ministration of different types of glycosaminoglycans prevents morphological renal alterations and albumi-nuria in diabetic rats. This study was designed to eva¬luate the effect of short term administration of nadro-parin calcium (a type of low molecular weight hepa-rin) on proteinuria and to measure heparan sulphate loss in the urine in a streptosotocin diabetic rat mo¬del. Twenty, twelve weeks old wistar rats were made diabetic using streptosotocin. One group of ten rats received nadroparin calcium 200 U/kgld, whilst the second group received. 0.1 cc saline/d as control. 24 hour urine samples were collected at the begining of the study and at the end of the 6th week for determi¬nation of creatinine clearence, heparan sulphate exc¬retion and microalbuminuria. Basal levels of microal-buminuria did not differ between nadroparin calcium and control groups (11 ± 13 mgld and 12.3 ±8 mgld respectively). At the end of the study microalbuminu-ria was significantly lower in the study group (2.8 ± 3.8 mgld and 28.5 ± 12 mgld respectively, p<0.05). Basal heparan sulphate excretion did not differ bet¬ween two groups (104.7 ± 66.5 [i^d and 128 ± 69.5 igld respectively). At the end of the study heparan sulphate excretion was significantly lower in the nadroparin calcium group (195 ± 96 mgld and 662 ±300 mgld respectively, p<0.01). In conclusion short term nadroparin calcium therapy may lead to reduction of microalbuminuria and heparan sulphate excretion by means of protection or replacement of the glomerular basement membrane anionic charge
Abstract (Original Language): 
Glukozaminoglikan metabolizma bozukluğu diabe-tik nefropati patogenezinde rol oynamakladır. Mikro-albüminüriye neden olan glomerüler bazal membran anyonik yük kaybı, idrarda glukozaminoglikan kaybı ile ilişkilidir. Diabetik rotlarda uzun süreli glukozaminoglikan tedavisinin hem morfolojik renal değişik¬likleri, hem de albüminüriyi önlediği bilinmektedir. Bu çalışma, kısa süreli nadroparin kalsiyum (düşük moleküler ağırlıklı heparin) tedavisinin renal fonksi¬yonlar, idrarda heparan sülfat ve albumin ekskresyo-nu üzerinde etkilerini araştırmak amacıyla planlan¬mıştır. Yirmi adet, oniki haftalık Wistar rat, strepto-zotosin ile diabetik hale getirilmiştir, on rattan olu¬şan birinci grup 200 U/kg/gün nadroparin kalsiyum tedavisi alırken, ikinci grupta kontrol olarak 0.1 cc serum fizyolojik verilmiştir. Hayvanların 24 saatlik kreatinin klirens, microalbüminüri ve heparan sülfat ekskresyonu ölçülmüştür. Nadroparin kalsiyum ve kontrol grupları arasında bazal mikroalbüminüri de¬ğerleri açısındanfark yoktur (11 ± 13 mglgün ve 12.3 ± 8 mglgün, sırasıyla). Çalışma sonunda tedavi gru¬bunda mikroalbüminüri kontrol grubuna oranla an¬lamlı ölçüde düşük bulunmuştur (2.8 ±3.8 mglgün ve 28.5 ± 12 mglgün sırasıyla, p<0.05). Çalışma baş¬langıcında heparan sülfat ekskresyonu her iki grup arasında farklılık göstermemekteyken (104.7 ± 66.5 [ig/gün ve 128 ± 69.5 [i-glgun, sırasıyla), tedavi so¬nunda nadroparin kalsiyum grubunda belirgin olarak düşük bulunmuştur (195 ± 96 [i-glgün ve 662 ± 300 [i^gun, sırasıyla, p<0.01). Sonuçta kısa süreli nadro-parin kalsiyum tedavisi idrarda heparan sülfat ve al-bümin ekskresyonunu belirgin olarak azaltmaktadır. Bu etki glomerül bazal membram anyonik yüklerinin korunması veya yerine konması ile ilişkili olabilir.
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