Myocardial fibrosis is one of the main pathological manifestations of diabetic cardiomyopathy (DCM). Spermine (SPM), a product of polyamine metabolism, plays an important role in many cardiac diseases including hypertrophy, ischemia, and infarction, but its role in diabetic myocardial fibrosis has not been clarified. This study aimed to investigate the role of polyamine metabolism, specifically SPM, in diabetic myocardial fibrosis and to explore the related mechanisms. We used intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in Wistar rats and high glucose (HG, 40 mM) stimulated cardiac fibroblasts (CFs) to established a type 1 diabetes (T1D) model in vivo and in vitro, which were pretreated with exogenous SPM (5 mg/kg per day and 5 μM). The results showed that hyperglycemia induced the expression of the key polyamine synthesis enzyme ornithine decarboxylase (ODC) decreased and the key catabolic enzyme spermidine/spermine N¹‐acetyltransferase (SSAT) increased compared with those in the control group. The body weight, blood insulin level, and cardiac ejection function were decreased, while blood glucose, heart weight, the ratio of heart weight to body weight, myocardial interstitial collagen deposition, and endoplasmic reticulum stress (ERS)‐related protein (glucose‐regulated protein‐78, glucose‐regulated protein‐94, activating transcription factor‐4, and C/EBP homology protein) expression in the T1D group were all significantly increased. HG also caused an increased expression of Wnt3, β‐catenin (in cytoplasm and nucleus), while Axin2 and phosphorylated β‐catenin decreased. Exogenous SPM improved the above changes caused by polyamine metabolic disorders. In conclusion, polyamine metabolism disorder occurs in the myocardial tissue of diabetic rats, causing myocardial fibrosis and ERS. Exogenous SPM plays a myocardial protective role via inhibiting of ERS and the canonical Wnt/β‐catenin signaling pathway.

中文翻译：

---

外源精胺通过抑制内质网应激和经典的Wnt信号通路来减轻糖尿病性心肌病的心肌纤维化。

心肌纤维化是糖尿病性心肌病（DCM）的主要病理表现之一。精胺（SPM）是多胺代谢的产物，在许多心脏疾病（包括肥大，局部缺血和梗死）中都起着重要作用，但其在糖尿病性心肌纤维化中的作用尚不清楚。这项研究旨在调查多胺代谢，特别是SPM在糖尿病性心肌纤维化中的作用，并探讨相关的机制。我们在Wistar大鼠中腹膜内注射链脲佐菌素（STZ，60 mg / kg）和高葡萄糖（HG，40 mM）刺激的心脏成纤维细胞（CFs）建立了体内和体外的1型糖尿病（T1D）模型。用外源SPM（每天5 mg / kg和5μM）预处理。^1个‐乙酰转移酶（SSAT）与对照组相比有所增加。体重，血液胰岛素水平和心脏射血功能降低，而血糖，心脏重量，心脏重量与体重之比，心肌间质胶原沉积和内质网应激（ERS）相关蛋白（葡萄糖调节T1D组中的蛋白78，葡萄糖调节蛋白94，激活转录因子4和C / EBP同源蛋白的表达均显着增加。HG还引起Wnt3，β-catenin（在细胞质和细胞核中）的表达增加，而Axin2和磷酸化的β-catenin减少。外源性SPM改善了上述多胺代谢紊乱引起的变化。总之，多胺代谢紊乱发生在糖尿病大鼠的心肌组织中，引起心肌纤维化和ERS。外源性SPM通过抑制ERS和经典的Wnt /β-catenin信号通路发挥心肌保护作用。