Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
Department of Anatomy, Histology and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
Open Vet J. 2024 Sep;14(9):2287-2293. doi: 10.5455/OVJ.2024.v14.i9.17. Epub 2024 Sep 30.
Cardiac fibrosis is often associated with various heart-related problems such as heart failure, atrial arrhythmia, and sudden cardiac death, making it a leading cause of death globally. Diabetes-associated fibrosis, on the other hand, is influenced by activated cardiac fibroblasts and potentially involves fibrosis-inducing activity of macrophages, cardiomyocytes, and vascular cells. Streptozotocin (STZ) is a known diabetogenic agent, but inadequate preclinical data in animal models hinders its clinical success.
This study aims to provide practical guidelines for STZ utilization in inducing diabetes-associated cardiac fibrosis.
The research was conducted using white rats () of the Wistar strain, induced with STZ at doses of 30 mg/KgBW and 50 mg/KgBW per injection. Observations were carried out in the 4th and 8th weeks, consisting of the measurement of blood sugar levels and the examination of heart muscle cell fibrosis. Subsequently, validation of STZ's affinity with inflammatory receptors causing diabetes pathology, such as TNFα and Bcl2, was performed.
The study results indicated that the administration of STZ led to an increase in random blood sugar levels and extensive fibrosis of heart muscle cells in mice. The optimal dose for the diabetes model experimented in this study was 50 mg/KgBW for 8 weeks. tests revealed an affinity for TNFα (PDB ID 2AZ5) and Bcl2 (PDB ID 6QGH).
Consequently, it can be concluded that administering STZ to mice at a dose of 50 mg/KgBW for 8 weeks is an effective inducer of a diabetes-associated cardiac fibrosis model.
心脏纤维化常与各种心脏相关问题相关，如心力衰竭、心房心律失常和心源性猝死，是全球主要死亡原因之一。另一方面，糖尿病相关的纤维化受激活的心肌成纤维细胞影响，可能涉及巨噬细胞、心肌细胞和血管细胞的纤维化诱导活性。链脲佐菌素 (STZ) 是一种已知的致糖尿病剂，但动物模型中的临床前数据不足阻碍了其临床成功。
本研究旨在为 STZ 在诱导糖尿病相关心脏纤维化中的应用提供实用指南。
研究使用 Wistar 品系的白色大鼠（），以 30mg/KgBW 和 50mg/KgBW/次的剂量注射 STZ。在第 4 周和第 8 周进行观察，包括血糖水平测量和心肌细胞纤维化检查。随后，验证 STZ 与引起糖尿病病理的炎症受体（如 TNFα 和 Bcl2）的亲和力。
研究结果表明，STZ 的给药导致随机血糖水平升高和小鼠心肌细胞广泛纤维化。本研究中糖尿病模型实验的最佳剂量为 50mg/KgBW，持续 8 周。测试显示对 TNFα（PDB ID 2AZ5）和 Bcl2（PDB ID 6QGH）具有亲和力。
因此，可以得出结论，向小鼠注射 STZ 剂量为 50mg/KgBW，持续 8 周，是诱导糖尿病相关心脏纤维化模型的有效方法。
