二甲双胍改善2型糖尿病诱导的左心室损伤中纤维化和血脂异常的ROS-p53-胶原蛋白轴。
Metformin ameliorates ROS-p53-collagen axis of fibrosis and dyslipidemia in type 2 diabetes mellitus-induced left ventricular injury.
作者信息
Al-Ani Bahjat, Alzamil Norah M, Hewett Peter W, Al-Hashem Fahaid, Bin-Jaliah Ismaeel, Shatoor Abdullah S, Kamar Samaa S, Latif Noha S Abdel, Haidara Mohamed A, Dawood Amal F
机构信息
Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
Department of Clinical Science, Family Medicine, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
出版信息
Arch Physiol Biochem. 2023 Jun;129(3):734-740. doi: 10.1080/13813455.2020.1869265. Epub 2021 Jan 13.
BACKGROUND
The link between oxidative stress (ROS), apoptosis (p53) and fibrosis (collagen) in type 2 diabetes mellitus (T2DM)-induced cardiac injury in the presence and absence of the antidiabetic drug, metformin has not been investigated before.
MATERIAL AND METHODS
T2DM was induced in rats by a combination of high carbohydrate and fat diets (HCFD) and streptozotocin (50 mg/kg) injection. The protection group started metformin (200 mg/kg) treatment 14 days prior to the induction of diabetes and continued on metformin and HCFD until being sacrificed at week 12.
RESULTS
Diabetes significantly induced blood levels of ROS and left ventricular p53 and collagen expression that was inhibited by metformin. Metformin also significantly reduced glycated haemoglobin and dyslipidemia induced by diabetes. In addition, a significant correlation between ROS-p53-collagen axis and glycaemia and hyperlipidaemia was observed.
CONCLUSIONS
These findings show that metformin provides substantial protection against diabetic cardiomyopathy-induced ROS-p53 mediated fibrosis and dyslipidemia.
背景
在存在和不存在抗糖尿病药物二甲双胍的情况下，2型糖尿病（T2DM）诱导的心脏损伤中氧化应激（ROS）、细胞凋亡（p53）和纤维化（胶原蛋白）之间的联系此前尚未被研究过。
材料与方法
通过高碳水化合物和高脂肪饮食（HCFD）联合链脲佐菌素（50mg/kg）注射诱导大鼠患T2DM。保护组在糖尿病诱导前14天开始二甲双胍（200mg/kg）治疗，并继续使用二甲双胍和HCFD，直至在第12周处死。
结果
糖尿病显著诱导血液中ROS水平以及左心室p53和胶原蛋白表达，而二甲双胍可抑制这些变化。二甲双胍还显著降低了糖尿病诱导的糖化血红蛋白和血脂异常。此外，观察到ROS-p53-胶原蛋白轴与血糖和高脂血症之间存在显著相关性。
结论
这些发现表明，二甲双胍可对糖尿病性心肌病诱导的ROS-p53介导的纤维化和血脂异常提供实质性保护。
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