Sains Malaysiana 53(6)(2024): 1321-1332

http://doi.org/10.17576/jsm-2024-5306-08

Determining the Time Points for the Development of Early and Advanced Stages of Diabetic Cardiomyopathy in Streptozotocin-Induced Type 1 Diabetes Mellitus Rat Model

(Menentukan Titik Masa untuk Pembentukan Tahap Awal dan Lanjutan KardiomiopatiDiabetes pada Model Tikus Diabetes Mellitus Jenis 1 Teraruh Streptozotocin)

FATIN FARHANA JUBAIDI¹, NUR LIYANA MOHAMMED YUSOF¹, SATIRAH ZAINALABIDIN²,

IZATUS SHIMA TAIB¹, ZARIYANTEY ABD HAMID¹ & SITI BALKIS BUDIN^1,*

¹Center for Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia

²Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia

Received: 9 February 2024/Accepted: 16 May 2024

Abstract

The characteristics of early and advanced stages of diabetic cardiomyopathy (DCM) are well-understood; however, the time points by which these stages are developed in animal models vary and depend on the hyperglycaemic status and duration of diabetes. This study was aimed to determine the time points for the development of early and advanced stages of DCM from the induction of type 1 diabetes mellitus by identifying the functional and histological changes that occurred. Type 1 diabetes was induced via streptozotocin injection, and rats were divided into 4-week and 8-week diabetic groups. A group of non-diabetic rats served as the normal control. Cardiac functions and structural changes were analysed. Results showed that after four weeks, all diabetic rats displayed early DCM characteristics, including pronounced left ventricular diastolic dysfunction and cardiomyocyte hypertrophy (P < 0.05) compared to the normal control. After eight weeks, there was a significant deterioration in both left ventricular systolic and diastolic function compared to the normal control, along with marked cardiomyocyte hypertrophy and myocardial fibrosis (P < 0.05), signifying the development of advanced DCM. In summary, this findings revealed the development of early and advanced stages of DCM at four weeks and eight weeks of diabetes respectively in diabetes melitus type 1 rat model.

Keywords: Diastolic dysfunction; fibrosis; hypertrophy; systolic dysfunction; type 1 diabetes mellitus

Abstrak

Ciri-ciri peringkat awal dan lanjut kardiomiopati diabetes (DCM) telah dikenalpasti; walau bagaimanapun, titik masa di mana peringkat ini terbentuk di dalam model haiwan adalah berbeza dan bergantung kepada status hiperglisemia dan tempoh diabetes. Kajian ini bertujuan untuk menentukan titik masa pembentukan peringkat awal dan lanjut DCM daripada aruhan diabetes mellitus jenis 1 dengan mengenal pasti perubahan fungsi dan histologi yang berlaku. Diabetes jenis 1 telah diaruh secara suntikan streptozotocin dan tikus dibahagikan kepada kumpulan diabetes 4 dan 8 minggu. Sementara itu, tikus bukan diabetes dijadikan kumpulan kawalan. Fungsi dan perubahan struktur jantung dianalisa. Hasil kajian menunjukkan pada empat minggu diabetes, semua tikus diabetes menunjukkan ciri-ciri awal DCM, termasuklah disfungsi diastolik ventrikel kiri dan hipertrofi kardiomiosit yang ketara (P <0.05) berbanding kumpulan normal. Selepas lapan minggu diabetes, terdapat kemerosotan yang ketara pada kedua-dua fungsi sistolik dan diastolik ventrikel kiri berbanding dengan kumpulan normal, dengan hipertrofi kardiomiosit dan fibrosis miokardium yang ketara (P <0.05), menunjukkan pembentukan DCM peringkat lanjut. Kesimpulannya, DCM peringkat awal berlaku pada empat minggu diabetes manakala DCM peringkat lanjut pula pada lapan minggu diabetes pada model tikus diabetes jenis 1.

Kata kunci: Diabetes melitus jenis 1; disfungsi diastolik; disfungsi sistolik; fibrosis; hipertrofi

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*Corresponding author; email: balkis@ukm.edu.my