Tip-2 diyabetes mellitusu olan hastalarda polinöropati gelişimi ile sarm1 ve hıf-1 alfa ekspresyonu arasındaki ilişkinin araştırılması
Küçük Resim Yok
Tarih
2024
Yazarlar
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Yayıncı
Tekirdağ Namık Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Tip-2 diyabetes mellitus (T2DM)'un neden olduğu mikrovasküler komplikasyonlardan en sık görülen distal simetrik polinöropati (DSPN)'nin günümüzde halen net bir tedavi protokolü bulunmamaktadır. Bundan dolayı bir yandan kişilerde; nöropatik ağrı, otonomik disfonksiyon, ayak ülserleri, amputasyon, artmış mortalite riski ve düşük yaşam kalitesi meydana gelirken, diğer yandan artan tedavi maliyetleri ve hospitalizasyonun uzamasına bağlı sağlık ekonomilerine ağır yükler binmektedir. Bu doktora tezinde, T2DM tanısı olup, DSPN'den muzdarip olguların steril alfa ve Toll/interlökin-1 reseptörü (TIR) motif içeren protein (SARM)-1 ve hipoksi ile indüklenebilir faktör-1 alfa (Hif-1?) gen ve protein ifade düzeylerinin değerlendirilebilmesi amaçlandı. Kontrollü randomize blok dizayna sahip bu araştırmada, kontrol grubu sağlıklı bireylerden oluşturuldu ve grup 1 olarak adlandırıldı. Çalışma gruplarında ise grup 2 olarak adlandırılan grupta sadece T2DM tanılı, grup 3'te T2DM ile birlikte DSPN tanısı olan ve grup 4'de bozulmuş glukoz toleransı (BGT) olan olgulardan oluşturuldu. Ardından tüm gruplarda yer alan bireylerin venöz kanlarında, aksonal dejenerasyonda temel bir komponent olduğu iddia edilen SARM1 ile Hif-1? gen ifadeleri ve protein düzeyleri ölçüldü. Elde edilen verilerin istatistiksel değerlendirmeleri esnasında, gruplar arası karşılaştırmalarda Varyans Analizi sonrası Tukey's Honestly Significant Test (HSD) çoklu karşılaştırma testinden faydalanılırken, değişkenler arasındaki ilişki Pearson Korelasyon testi ile kontrol edildi. Gruplararası karşılaştırmalarda, grupların SARM1 gen ifadesi üzerine etkisi istatistiksel olarak anlamlı bulundu (P<0,05). Ancak, Hif-1? gen ifadesini üzerine olumsuz yönde değişiklikler tespit edilmesine rağmen, bu değişimlerin istatistiksel olarak anlamsız idi (P>0,05). Hem SARM1 hem de Hif-1?'nın protein düzeylerindeki değişimler değerlendirildiğinde ise tüm protein düzeylerindeki bu değişimlerin, istatistiksel olarak anlamlı (p<0,05) olduğu anlaşıldı. Ek olarak SARM1 ile Hif-1? arasında zayıf negatif yönde bir korelasyon ilişkisi olduğu görüldü ancak bu ilişkinin istatistiksel olarak anlamlı olmadığı anlaşıldı (P>0,05). Bu araştırmadan elde edilen bulguların, gelecekte T2DM ile ilişkili DSPN'li olguların hedef tedavilerine katkı sağlayabileceği inancındayız. Ek olarak, SARM1'in inhibe ve Hif-1?'nın korunacağı veya düşük ya da yüksek değerde ise normoksik koşullara indükleneceği manipülatif nörofarmakolojik ajanlar geliştirilebilirse, akson dejenerasyonuna bağlı DSPN'nin de önleyebileceğini varsayıyoruz. Anahtar kelimeler: Akson dejenerasyonu, Bozulmuş glukoz toleransı, Distal simetrik polinöropati, Hif-1?, SARM1, Tip-2 Diabetes Mellitus.
Despite the existence of numerous studies on the subject, there is still no clear treatment protocol for distal symmetric polyneuropathy (DSPN), which is the most common microvascular complication caused by type-2 diabetes mellitus (T2DM). Consequently, while individuals experience neuropathic pain, autonomic dysfunction, foot ulcers, amputation, increased mortality risk and low quality of life, the financial burden on healthcare expenditure is significant due to increased treatment costs and prolonged hospitalisation. The objective of this doctoral thesis was to evaluate the gene and protein expression levels of sterile alpha and Toll/interleukin-1 receptor (TIR) motif-containing protein (SARM)-1 and hypoxia-inducible factor-1 alpha (HIF-1?) in patients diagnosed with DSPN who were also diagnosed with T2DM. The study was designed as a controlled, randomized block type, with the control group, designated as Group 1, comprising healthy individuals. The study groups were as follows: Group 2 consisted of cases with a T2DM diagnosis alone; Group 3 consisted of cases with a DSPN diagnosis in addition to T2DM; and Group 4 consisted of cases with impaired glucose tolerance (IGT). Subsequently, the expressions and protein levels of the SARM1 and HIF-1? genes, which are purported to be essential components in axonal degeneration, were quantified in the venous blood of individuals across all groups. During the statistical analysis of the obtained data, Tukey's Honestly Significant Test (HSD) was employed as a multiple comparison test following the Analysis of Variance in comparisons between groups. Additionally, the relationship between the variables was evaluated with the Pearson Correlation test. In intergroup comparisons, the effect of the groups on SARM1 gene expression was found to be statistically significant (P<0.05). However, although negative changes were detected on Hif-1? gene expression, these changes were statistically insignificant (P>0.05). When the changes in the protein levels of both SARM1 and Hif-1? were evaluated, it was understood that these changes in all protein levels were statistically significant (P <0.05). Furthermore, a weak negative correlation was observed between SARM1 and Hif-1?, although this relationship was not statistically significant (P>0.05). It is believed that the findings of this study may contribute to the development of targeted treatments for patients with DSPN associated with T2DM in the future. Furthermore, it is postulated that the prevention of DSPN development due to axon degeneration necessitates the use of neuropharmacological agents to inhibit SARM1 and protect Hif-1?. Key words: Axon degeneration, Distal Symmetric Polyneuropathy, Hif-1?, Impaired glucose tolerance, SARM1, Type-2 Diabetes Mellitus.
Despite the existence of numerous studies on the subject, there is still no clear treatment protocol for distal symmetric polyneuropathy (DSPN), which is the most common microvascular complication caused by type-2 diabetes mellitus (T2DM). Consequently, while individuals experience neuropathic pain, autonomic dysfunction, foot ulcers, amputation, increased mortality risk and low quality of life, the financial burden on healthcare expenditure is significant due to increased treatment costs and prolonged hospitalisation. The objective of this doctoral thesis was to evaluate the gene and protein expression levels of sterile alpha and Toll/interleukin-1 receptor (TIR) motif-containing protein (SARM)-1 and hypoxia-inducible factor-1 alpha (HIF-1?) in patients diagnosed with DSPN who were also diagnosed with T2DM. The study was designed as a controlled, randomized block type, with the control group, designated as Group 1, comprising healthy individuals. The study groups were as follows: Group 2 consisted of cases with a T2DM diagnosis alone; Group 3 consisted of cases with a DSPN diagnosis in addition to T2DM; and Group 4 consisted of cases with impaired glucose tolerance (IGT). Subsequently, the expressions and protein levels of the SARM1 and HIF-1? genes, which are purported to be essential components in axonal degeneration, were quantified in the venous blood of individuals across all groups. During the statistical analysis of the obtained data, Tukey's Honestly Significant Test (HSD) was employed as a multiple comparison test following the Analysis of Variance in comparisons between groups. Additionally, the relationship between the variables was evaluated with the Pearson Correlation test. In intergroup comparisons, the effect of the groups on SARM1 gene expression was found to be statistically significant (P<0.05). However, although negative changes were detected on Hif-1? gene expression, these changes were statistically insignificant (P>0.05). When the changes in the protein levels of both SARM1 and Hif-1? were evaluated, it was understood that these changes in all protein levels were statistically significant (P <0.05). Furthermore, a weak negative correlation was observed between SARM1 and Hif-1?, although this relationship was not statistically significant (P>0.05). It is believed that the findings of this study may contribute to the development of targeted treatments for patients with DSPN associated with T2DM in the future. Furthermore, it is postulated that the prevention of DSPN development due to axon degeneration necessitates the use of neuropharmacological agents to inhibit SARM1 and protect Hif-1?. Key words: Axon degeneration, Distal Symmetric Polyneuropathy, Hif-1?, Impaired glucose tolerance, SARM1, Type-2 Diabetes Mellitus.
Açıklama
Sağlık Bilimleri Enstitüsü, Nöroloji Ana Bilim Dalı, Klinik Nörofizyoloji Bilim Dalı
Anahtar Kelimeler
Nöroloji, Neurology
