Publication: Sodyum glukoz ortak taşıyıcı inhibitörlerinin tip 2 diyabetes mellitus oluşturulmuş sıçanların kalp dokusundaki microrna’lar üzerine etkilerinin incelenmesi
Abstract
Amaç: Diabetes Mellitus (DM), son yıllarda küresel bir sorun haline gelmiş ve beraberinde gelişen komplikasyonlarla birlikte önemi her geçen gün daha da artmıştır. Tip 2 DM (T2DM) tedavisinde kullanılan Empagliflozin (EMPA) ve Dapagliflozin (DAPA), böbreklerden glukozun geri emilimini inhibe ederek kan glukozunu düşürmekte ve klinikte oldukça yaygın olarak kalple ilişkili durumlarda DM olmaksızın bile kullanılmaktadır. Ayrıca bu ilaçlar kardiyovasküler olay riskini ve buna bağlı mortaliteyi de azaltır. Bu çalışmada, nikotinamid/ streptozotosin ile indüklenen T2DM sıçanların kalp dokusunda EMPA ve DAPA’nın farklı miRNA ekspresyonları üzerindeki etkilerinin araştırılarak etki mekanizmalarıyla ilişkili farklı yolakların aydınlatılması amaçlanmıştır. Gereç ve Yöntem: 3-4 aylık Sprague-Dawley sıçanlar (dişi/ erkek) dört gruba ayrılmıştır; Kontrol, T2DM, EMPA ve DAPA. Sıçanların vücut ağırlıkları ve kan glukoz değerleri haftalık olarak ölçülmüştür. Serum ve kalp dokusunda interlökin-1β (IL-1β), süperoksit dismutaz (SOD), ileri glikasyon son ürünleri reseptörü (İGÜR) ve kardiyak troponin I (kTnI) düzeyleri ELİSA analizleri ile incelenmiştir. RT-PCR, diyabetik sıçanların kalp dokusundaki miR-223, miR-373, miR-22, miR-9, miR-146a, miR-21, miR-144, miR-221, miR-133a ve miR-34a olmak üzere on farklı miRNA'nın ekspresyon seviyelerini analiz etmek için kullanılmıştır. Bulgular: EMPA ve DAPA tedavilerinin inflamasyonda ve histopatolojik incelemelerde iyileşme sağladığı bulunmuştur. miRNA ekspresyonları incelendiğinde miR-223, miR-373, miR-22, miR-9, miR-146a, miR-21, miR-144, miR-221 ve miR-34a ekspresyonları Kontrol grubunda anlamlı derecede yüksektir. Ayrıca miR-146a ve miR-34a düzeyleri EMPA grubunda T2DM grubuna kıyasla yüksek iken miR-146a ekspresyonunun DAPA grubunda T2DM grubuna kıyasla artışı istatistiksel olarak anlamlı görülmüştür. Sonuç: EMPA ve DAPA kalpte miRNA ekspresyonlarını düzenleyici etkiye sahiptir ve kalpteki koruyucu etkilerine dair ekspresyon farklılıkları bulunan miRNA ile ilişkili genler üzerinde daha detaylı çalışılma yapılmasının gerekliliği düşünülmüştür.
Objective: Diabetes Mellitus (DM) has become a global problem in recent years and its importance has increased day by day with its accompanying complications. Empagliflozin (EMPA) and Dapagliflozin (DAPA), used in the treatment of Type 2 DM (T2DM), reduce blood glucose by inhibiting the reabsorption of glucose from the kidneys and are widely used clinically in heart-related conditions without DM. In addition, these drugs reduce the risk of cardiovascular events and related mortality. This study aimed to shed light on the pathway differences related to their mechanisms of action by investigating the effects of EMPA and DAPA on different miRNA expressions in the heart tissue of T2DM rats induced by nicotinamide/ streptozotocin. Materials and Methods: Sprague-Dawley rats (female/ male) of 3-4 months of age are divided into four groups; Control, T2DM, EMPA, and DAPA. The body weights and blood glucose values of the rats were measured weekly. The interleukine-1β (IL-1β), superoxide dismutase (SOD), receptor for advanced glycation end-products (RAGE), and cardiac troponin I (cTnI) levels in serum and heart tissue were examined by ELİSA analyses. RT-PCR was used to analyze the expression levels of ten different miRNAs including miR-223, miR-373, miR-22, miR-9, miR-146a, miR-21, miR-144, miR-221, miR-133a and miR-34a in the heart tissue of diabetic rats. Results: EMPA and DAPA treatments were found to provide improvement in inflammation and histopathological examinations. When miRNA expressions are examined, miR-223, miR-373, miR-22, miR-9, miR-146a, miR-21, miR-144, miR-221, and miR-34a expressions are significantly higher in the control group. In addition, while miR-146a and miR-34a levels are higher in the EMPA group compared to the T2DM group, the increase in miR-146a expression in the DAPA group compared to the T2DM group is statistically significant. Conclusion: EMPA and DAPA have a regulatory effect on miRNA expressions in the heart, and miRNA-related genes with expression differences regarding their protective effects in the heart should be studied in more detail.
Objective: Diabetes Mellitus (DM) has become a global problem in recent years and its importance has increased day by day with its accompanying complications. Empagliflozin (EMPA) and Dapagliflozin (DAPA), used in the treatment of Type 2 DM (T2DM), reduce blood glucose by inhibiting the reabsorption of glucose from the kidneys and are widely used clinically in heart-related conditions without DM. In addition, these drugs reduce the risk of cardiovascular events and related mortality. This study aimed to shed light on the pathway differences related to their mechanisms of action by investigating the effects of EMPA and DAPA on different miRNA expressions in the heart tissue of T2DM rats induced by nicotinamide/ streptozotocin. Materials and Methods: Sprague-Dawley rats (female/ male) of 3-4 months of age are divided into four groups; Control, T2DM, EMPA, and DAPA. The body weights and blood glucose values of the rats were measured weekly. The interleukine-1β (IL-1β), superoxide dismutase (SOD), receptor for advanced glycation end-products (RAGE), and cardiac troponin I (cTnI) levels in serum and heart tissue were examined by ELİSA analyses. RT-PCR was used to analyze the expression levels of ten different miRNAs including miR-223, miR-373, miR-22, miR-9, miR-146a, miR-21, miR-144, miR-221, miR-133a and miR-34a in the heart tissue of diabetic rats. Results: EMPA and DAPA treatments were found to provide improvement in inflammation and histopathological examinations. When miRNA expressions are examined, miR-223, miR-373, miR-22, miR-9, miR-146a, miR-21, miR-144, miR-221, and miR-34a expressions are significantly higher in the control group. In addition, while miR-146a and miR-34a levels are higher in the EMPA group compared to the T2DM group, the increase in miR-146a expression in the DAPA group compared to the T2DM group is statistically significant. Conclusion: EMPA and DAPA have a regulatory effect on miRNA expressions in the heart, and miRNA-related genes with expression differences regarding their protective effects in the heart should be studied in more detail.