School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, 250200, China.
Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China.
Curr Med Sci. 2020 Feb;40(1):35-47. doi: 10.1007/s11596-020-2144-x. Epub 2020 Mar 13.
Type 1 diabetes mellitus (T1DM) is associated with an increased risk of diabetic cardiomyopathy (DCM). Nuclear factor kappa B (NF-κB) and Wnt/β-catenin/GSK3β have been demonstrated to play pathogenic roles in diabetes. In this study, we evaluated the roles of these two pathways in T1DM-induced cardiomyopathy in rats. Streptozotocin (STZ)-induced type 1 diabetic rats were treated with pyrrolidine dithiocarbamate (PDTC) or meisoindigo (Me) to inhibit NF-κB and Wnt/β-catenm/GSK3β respectively for 4 or 8 weeks. As compared with untreated diabetic rats, treatment with either PDTC or Me partly attenuated the myocardial hypertrophy and interstitial fibrosis, improved cardiac function, and exhibited reduction in inflammatory reaction. In addition, we found that inhibiting NF-κB and Wnt/β-catenin/GSK3β pathways could regulate glucose and lipid metabolism. The effects were associated with the decrease of NF-κB activity and the downregulation of some proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-2. Our data suggested that the activities of NF-κB and Wnt/β-catenin/GSK3β pathways were both increased and inhibiting NF-κB and Wnt/β-catenin/GSK3β signaling pathways might improve myocardial injury in T1DM rats.
1 型糖尿病（T1DM）与糖尿病心肌病（DCM）的风险增加有关。核因子 kappa B（NF-κB）和 Wnt/β-catenin/GSK3β 已被证明在糖尿病中发挥致病作用。在这项研究中，我们评估了这两条通路在 T1DM 诱导的大鼠心肌病中的作用。链脲佐菌素（STZ）诱导的 1 型糖尿病大鼠用吡咯烷二硫代氨基甲酸盐（PDTC）或美索吲哚（Me）分别抑制 NF-κB 和 Wnt/β-catenm/GSK3β 4 或 8 周。与未治疗的糖尿病大鼠相比，用 PDTC 或 Me 治疗部分减轻了心肌肥大和间质纤维化，改善了心脏功能，并减少了炎症反应。此外，我们发现抑制 NF-κB 和 Wnt/β-catenin/GSK3β 通路可以调节糖和脂质代谢。这些作用与 NF-κB 活性的降低以及一些促炎细胞因子（包括肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-2）的下调有关。我们的数据表明，NF-κB 和 Wnt/β-catenin/GSK3β 通路的活性均增加，抑制 NF-κB 和 Wnt/β-catenin/GSK3β 信号通路可能改善 T1DM 大鼠的心肌损伤。
