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العنوان
Study of long non-coding RNA and mitochondrial dysfunction in diabetic rats /
المؤلف
Kamal, Haytham Khalid Ahmed.
هيئة الاعداد
باحث / هيثم خالد أحمد كمال
مشرف / عزة حسن أبوغالية
مشرف / عمرو سيد محمود مصطفى
مشرف / نهى نوح لاشين
مشرف / وائل محمد العياط
تاريخ النشر
2021.
عدد الصفحات
188 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الكيمياء الحيوية (الطبية)
تاريخ الإجازة
1/1/2021
مكان الإجازة
جامعة عين شمس - كلية الطب - الكيمياء الحيوية الطبية و البيولوجيا الجزيئية
الفهرس
Only 14 pages are availabe for public view

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from 185

Abstract

Diabetes mellitus has become one of the major healthcare problems worldwide. Cardiovascular disease is a major cause of mortality in DM type 1 (T1DM) (Fan et al., 2019).
Mitochondria are dynamic organelles that move, fuse, divide, and die. Mitochondria undergo fission and fusion to form dynamic interconnecting networks. The fusion and fission processes occur in a constant and balanced manner to adapt the mitochondrial network morphology to the metabolic needs of the cell (Duraisamy et al., 2019).
The lncRNAs are implicated in development and progression of a number of different diseases. The H19 gene produces a non-coding RNA. The lncRNA H19 acts as miRNA precursor as exon 1 of H19 encodes two conserved miRNAs: miR-675-3p and miR-675-5p. Another function is to act as microRNA ‘sponge’ through its miRNA binding sites (Han et al., 2016).
The current study was carried out at Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University (2018-2020) in collaboration with physiology department, Faculty of Medicine, Ain Shams University. The study was approved by Research Ethics Committee (REC), Faculty of Medicine, Ain Shams University. This study aimed to evaluate the functional role of LncRNA H-19 and its relation to Mfn-2 expression in diabetic rats with cardiovascular and renal complications.
The current study was performed on 24 adult male albino rats that were equally divided into two groups; group 1 (control): injected once with 0.05 M citrate buffer, intra-peritoneal (IP). group 2 (diabetic): injected IP once with 40 mg/kg body weight STZ dissolved in 0.05 M citrate buffer.
 All groups were subjected to:
1- Measurement of random blood glucose level in rat tail blood 3 days after induction of diabetes to confirm being diabetic. The measurement was repeated every 2 weeks throughout the study duration.
2- Measurement of arterial blood pressure.
3- Urine samples collection (24-hour samples).
4- Echocardiogram monitoring and ECG recording.
5- Sacrifaction of rats was followed by blood and tissue sampling, histological examination (light and electron microscope).
6- Spectrophotometric assessment of biochemical parameters.
7- Measurement of expression of LncRNA H19 and Mfn-2 using real-time PCR.
 The results of the current study revealed the following:
Diabetic rats had significantly lower systolic, diastolic blood pressure, heart rate and P wave voltage compared to control rats. Diabetic rats had significantly higher R wave voltage compared to control rats.
The diabetic rats’ whole-body weights were significantly lower than control rats. Moreover, their whole cardiac weights, atrial and right ventricular weights were significantly lower than control rats. On the other side diabetic rats’ left ventricle/ body weight ratio was significantly higher than control rats.
Diabetic rats had significantly higher serum levels of glucose, TAG, cholesterol, LDL-cholesterol, CK-MB, serum creatinine, BUN, urine albumin and albumin/creatinine ratio compared to control rats. Diabetic rats had significantly lower creatinine clearance, serum albumin and urine creatinine compared to control rats.
Expression of LncRNA H19 and Mfn-2 mRNA in cardiac tissues showed no significant statistical difference between diabetic and control rats. The diabetic kidney tissues had significantly lower expression levels of mRNA Mfn-2 compared to control rats. There was significant negative correlation between the expression of Mfn-2 and H19 in diabetic cardiac tissues, and nonsignificant negative correlation in diabetic kidney tissues. The decreased expression of Mfn-2 was positively correlated with serum albumin levels and negatively correlated with serum LDL-cholesterol levels in diabetic rats. Significant positive correlation was detected between lncRNA H19 expression and serum HDL level.