Adiposit türevli kök hücre uygulamasının streptozotosin ile indüklenmiş diyabetik nöropati üzerindeki etkilerinin incelenmesi
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Tarih
2018
Yazarlar
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Yayıncı
Ege Üniversitesi, Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Diabetes mellitus' un en yaygın görülen dejeneratif komplikasyonu, diyabetik nöropati (DN)' dir. Periferik sinir hasarı sonucu oluşan DN, ayaklarda ve ellerde uyuşukluk, halsizlik, şiddetli ağrı ve ülserasyonlara neden olur. Günümüzde DN, yüksek morbitide oranı ve artan prevalans değerleri ile önemli sağlık sorunları arasında yer almaktadır. Bilinen yaygınlığına rağmen DN' de kullanılan tek etkili tedavi kan glukoz kontrolü ve ağrı yönetimidir. Çalışmamızın amacı, adipoz türevli kök hücre (AT-KH) uygulamasının, DN' de siyatik sinirler üzerindeki etkisini, elektromiyografik (EMG), histokimyal ve immünofloresan analizler ile incelemekti. Toplam 27 BALB / c fare; kontrol grubu, DM (Diyabet + Serum fizyolojik tedavi) grubu ve AT-KH (Diyabet + ADSC tedavisi) grubu olmak üzere 3'e ayrıldı. EMG' de, siyatik sinir bileşik kas aksiyon potansiyeli (BKAP) amplitüdü, diyabet grubunda kontrol grubuna göre daha düşük iken, distal latans daha yüksekti. BKAP amplitüdü, diyabet grubuna göre, AT-KH grubu siyatik sinirinde daha yüksekti. Distal latans ise diyabet grubuna göre, AT-KH grubu siyatik sinirinde daha düşüktü. Diyabetik farelerin siyatik sinir ışık mikroskobu bulgularında, aksonal atrofi, endonöryal ödem, polimorfik nükleer lökosit (PMNL) infiltrasyonu, aksonal miyelinlerin vakuolizasyonu ve lamellar ayrılmalar (miyelin yıkımları) saptandı. Adipoz türevli kök hücre tedavisi uygulanan hayvan dokularının histolojik incelemelerinde, miyelinli ve miyelinsiz fibrillerin mikroskobik morfolojilerinin önemli oranda iyileştiği, PMNL infiltrasyonu ve demiyelinizasyonun ise ciddi anlamda azaldığı gözlendi. Aksonal dejenerasyona rastlanmadı. Miyelinlerde ki lameller ayrışma daha az belirgindi. Floresans mikroskobu incelemeleri, kas içine transplante edilmiş AT-KH' lerin, seçilimli olarak siyatik sinirlerde lokalize olduğunu gösterdi. AT-KH transplantasyonu, siyatik sinirlerde diyabetle bozulan S100, cdk2, NGF, DHH ve VEGF protein ekspresyonunu arttırdı. Kontrol grubuyla karşılaştırıldığında VEGF seviyelerinde önemli değişiklikler gözlenmedi. Bu çalışmada bulgularımız, transplante edilen ATKH' lerin; schwann hücreleri üzerindeki sinyal düzenleyici etkileri, nörotrofik davranışları ve miyelinizasyonu restore edebilme yetenekleri ile DN' yi iyileştirdiğini önermektedir.
Diabetic neuropathy (DN) is the most common degenerative complication associated with diabetes mellitus. DN, a result of damage to peripheral nerves, often causes numbness, weakness, severe pain and ulcerations, usually in feet and hands. DN is one of the important health problems of today with its high morbitide ratio and increasing prevalence values. Despite widespread cognizance of DN, the only effective treatments are blood glucose control and pain management. The aim of our study was to determine the effect of adipose derived stem cell (ADSC) therapy on sciatic nerves in diabetic neuropathy using electromyographic (EMG), histochemical and immunofluorescence analyses. A total of 27 BALB/c mice were randomly divided into 3 groups: control group, DM (Diabetes + Serum physiologic treatment) group and AT-KH (Diabetes + ADSC treatment) group. In EMG, compound muscle action potential (CMAP) amplitude in the sciatic nerves was lower but distal latency were higher in the diabetes group compared with the control group. CMAP amplitude in the sciatic nerves was higher in the AT-KH group compared with the diabetes group. Distal latency in the sciatic nerve were lower in the AT-KH group compared with the diabetes group. Sciatic nerve light microscopy findings of diabetic mice showed axonal atrophy, endoneurial oedema, polimorf nuclear leukocyte (PMNL) infiltration, vacuolization and lamellar separation of axonal myelins (myelin destructions). Histologic examination of the tissues in animals treated ADSC showed remarkable improvement in microscopic morphology of myelinated and non-myelinated fibers, PMNL infiltration and demiyelinization decreased seriously. Axonal degeneration was not observed. Lamellar separation of myelins was less obvious. Fluorescence microscopy analyses demonstrated that intramuscularly transplanted ADSC, selectively localized in the sciatic nerves. Transplantation of ADSC increased protein expression of S100, cdk2, NGF, DHH and VEGF that impaired with diabetes in sciatic nerves. VEGF levels did not demonstrate significant changes compared with the Control group. In the present study, our findings suggest that ADSC transplantation improved DN through signal-regulatory effect on schwann cell, neurotrophic actions and restoration of myelination.
Diabetic neuropathy (DN) is the most common degenerative complication associated with diabetes mellitus. DN, a result of damage to peripheral nerves, often causes numbness, weakness, severe pain and ulcerations, usually in feet and hands. DN is one of the important health problems of today with its high morbitide ratio and increasing prevalence values. Despite widespread cognizance of DN, the only effective treatments are blood glucose control and pain management. The aim of our study was to determine the effect of adipose derived stem cell (ADSC) therapy on sciatic nerves in diabetic neuropathy using electromyographic (EMG), histochemical and immunofluorescence analyses. A total of 27 BALB/c mice were randomly divided into 3 groups: control group, DM (Diabetes + Serum physiologic treatment) group and AT-KH (Diabetes + ADSC treatment) group. In EMG, compound muscle action potential (CMAP) amplitude in the sciatic nerves was lower but distal latency were higher in the diabetes group compared with the control group. CMAP amplitude in the sciatic nerves was higher in the AT-KH group compared with the diabetes group. Distal latency in the sciatic nerve were lower in the AT-KH group compared with the diabetes group. Sciatic nerve light microscopy findings of diabetic mice showed axonal atrophy, endoneurial oedema, polimorf nuclear leukocyte (PMNL) infiltration, vacuolization and lamellar separation of axonal myelins (myelin destructions). Histologic examination of the tissues in animals treated ADSC showed remarkable improvement in microscopic morphology of myelinated and non-myelinated fibers, PMNL infiltration and demiyelinization decreased seriously. Axonal degeneration was not observed. Lamellar separation of myelins was less obvious. Fluorescence microscopy analyses demonstrated that intramuscularly transplanted ADSC, selectively localized in the sciatic nerves. Transplantation of ADSC increased protein expression of S100, cdk2, NGF, DHH and VEGF that impaired with diabetes in sciatic nerves. VEGF levels did not demonstrate significant changes compared with the Control group. In the present study, our findings suggest that ADSC transplantation improved DN through signal-regulatory effect on schwann cell, neurotrophic actions and restoration of myelination.
Açıklama
Anahtar Kelimeler
Diyabetik Nöropati, Adipoz Türevli Kök Hücre, Transplantasyon, Miyelin, Siyatik Sinir, Diabetic Neuropathy, Adipose Derived Stem Cell, Transplantation, Myelination, Sciatic Nerve
