Vilella Rocchina, Izzo Simona, Naponelli Valeria, Savi Monia, Bocchi Leonardo, Dallabona Cristina, Gerra Maria Carla, Stilli Donatella, Bettuzzi Saverio
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy.
Pharmaceuticals (Basel). 2022 Oct 28;15(11):1337. doi: 10.3390/ph15111337.
Green tea catechins are known to promote mitochondrial function, and to modulate gene expression and signalling pathways that are altered in the diabetic heart. We thus evaluated the effectiveness of the in vivo administration of a standardized green tea extract (GTE) in restoring cardiac performance, in a rat model of early streptozotocin-induced diabetes, with a focus on the underlying mechanisms. Twenty-five male adult Wistar rats were studied: the control (n = 9), untreated diabetic animals (n = 7) and diabetic rats subjected to daily GTE administration for 28 days (n = 9). Isolated ventricular cardiomyocytes were used for ex vivo measurements of cell mechanics and calcium transients, and molecular assays, including the analysis of functional protein and specific miRNA expression. GTE treatment induced an almost complete recovery of cardiomyocyte contractility that was markedly impaired in the diabetic cells, by preserving mitochondrial function and energy availability, and modulating the expression of the sarcoplasmic reticulum calcium ATPase and phospholamban. Increased Sirtuin 1 (SIRT1) expression and activity substantially contributed to the observed cardioprotective effects. The data supported the hypothesis that green tea dietary polyphenols, by targeting SIRT1, can constitute an adjuvant strategy for counteracting the initial damage of the diabetic heart, before the occurrence of diabetic cardiomyopathy.
已知绿茶儿茶素可促进线粒体功能,并调节糖尿病心脏中发生改变的基因表达和信号通路。因此,我们在早期链脲佐菌素诱导的糖尿病大鼠模型中,评估了体内给予标准化绿茶提取物(GTE)对恢复心脏功能的有效性,并重点研究了其潜在机制。研究了25只成年雄性Wistar大鼠:对照组(n = 9)、未治疗的糖尿病动物(n = 7)以及每天给予GTE持续28天的糖尿病大鼠(n = 9)。分离的心室心肌细胞用于体外测量细胞力学和钙瞬变,以及分子分析,包括功能性蛋白质和特定miRNA表达的分析。GTE治疗通过保留线粒体功能和能量供应,并调节肌浆网钙ATP酶和受磷蛋白的表达,使糖尿病细胞中明显受损的心肌细胞收缩力几乎完全恢复。沉默调节蛋白1(SIRT1)表达和活性的增加对观察到的心脏保护作用有很大贡献。这些数据支持了以下假设:绿茶膳食多酚通过靶向SIRT1,可在糖尿病性心肌病发生之前,构成一种对抗糖尿病心脏初始损伤的辅助策略。