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链脲佐菌素诱导 BALB/c 小鼠糖尿病模型不同器官的核和线粒体 DNA 损伤。

Damage to Nuclear and Mitochondrial DNA in Different Organs in Streptozotocin-Induced Diabetes Models in BALB/c Mice.

机构信息

V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2023 Jan;174(3):349-353. doi: 10.1007/s10517-023-05717-1. Epub 2023 Feb 1.

Abstract

Male BALB/c mice with streptozotocin-induced diabetes mellitus were used to study nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage using comet DNA assay and real-time PCR, respectively. In animals receiving single injection of streptozotocin in a dose of 200 mg/kg, severe hyperglycemia was observed on days 10 and 21 of the experiment, while after 5-fold administration of streptozotocin in a dose of 40 mg/kg, it developed on days 14 and 28. DNA damage and the level of atypical DNA comets in the liver increased both on days 10 and 21 after single administration of streptozotocin, and on days 14 and 28 after repeated administrations. The level of atypical DNA comets on day 21 after a single administration of streptozotocin increased in the kidneys, but not in the brain, testes, and pancreas. Real-time PCR revealed mtDNA damage in the liver, kidney, and pancreatic cells of mice with streptozotocin-induced diabetes. Thus, these animal models were found to reproduce pathognomic signs of diabetes, hyperglycemia, and nDNA damage; mtDNA damage was also detected.

摘要

雄性 BALB/c 糖尿病小鼠通过彗星 DNA 分析和实时 PCR 分别用于研究核 DNA(nDNA)和线粒体 DNA(mtDNA)损伤。在接受 200mg/kg 链脲佐菌素单次注射的动物中,在实验的第 10 天和第 21 天观察到严重的高血糖,而在接受 40mg/kg 5 倍剂量链脲佐菌素注射后,在第 14 天和第 28 天出现高血糖。在单次给予链脲佐菌素后的第 10 天和第 21 天,肝脏中的 DNA 损伤和非典型 DNA 彗星的水平均增加,而在重复给予后的第 14 天和第 28 天也增加。在单次给予链脲佐菌素后的第 21 天,肾脏中的非典型 DNA 彗星水平增加,但在大脑、睾丸和胰腺中没有增加。实时 PCR 显示,链脲佐菌素诱导的糖尿病小鼠的肝脏、肾脏和胰腺细胞中存在 mtDNA 损伤。因此,这些动物模型复制了糖尿病、高血糖和 nDNA 损伤的特征性表现,并且还检测到 mtDNA 损伤。

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