Mesenchymal stem cells improve cardiac function in diabetic rats by reducing cardiac injury biomarkers and downregulating JAK/STAT/iNOS and iNOS/Apoptosis signaling pathways

IF 3.8 3区 医学 Q2 CELL BIOLOGY Molecular and Cellular Endocrinology Pub Date : 2024-05-24 DOI:10.1016/j.mce.2024.112280
Thoraya Mohamed Elhassan A-Elgadir , Ayed A. Shati , Saif Aboud Alqahtani , Hasnaa A. Ebrahim , Hailah M. Almohaimeed , Asmaa M. ShamsEldeeen , Mohamed A. Haidara , Samaa S. Kamar , Amal F. Dawood , Mahmoud H. El-Bidawy
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Abstract

Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 106 cells/rat doses.

A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index).

Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways.

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间充质干细胞通过减少心脏损伤生物标志物和下调 JAK/STAT/iNOS 和 iNOS/Apoptosis 信号通路,改善糖尿病大鼠的心脏功能
心血管并发症是2型糖尿病(T2DM)的常见表现,通常是导致死亡的主要原因。本研究旨在揭示间充质干细胞(MSCs)对糖尿病心脏功能障碍的潜在治疗作用的内在机制。24只雄性Wistar大鼠被随机分配到三组中的一组。对照组接受标准实验室饲料,T2DM组在高脂饮食(HFD)预处理3周后接受单剂量45毫克/公斤体重的链脲佐菌素(STZ)。确诊 T2DM 八周后,大鼠被分为两组:T2DM 模型组和 T2DM + 间充质干细胞组。给药两周后,大鼠的胰岛素抵抗静态模型评估(HOMA-IR)和血脂异常明显改善。服用间叶干细胞可改善血脂异常、心脏损伤生物标志物的改变(p ≤ 0.0001)、Janus 激酶 2/信号转导和激活转录 3(JAK2/STAT3)/诱导一氧化氮合酶(iNOS)和 iNOS/细胞凋亡信号通路的下调。我们的研究结果表明,间充质干细胞可通过降低血脂异常和胰岛素抵抗、抑制氧化应激和炎症、下调 JAK2/STAT3/iNOS 和 iNOS/Aoptosis 信号通路,改善糖尿病心肌病相关的心脏功能障碍。
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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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