Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, China.
Department of Foot and Ankle Surgery, Xi'an Honghui Hospital, China.
Biochem Biophys Res Commun. 2021 Mar 26;546:29-34. doi: 10.1016/j.bbrc.2021.01.086. Epub 2021 Feb 6.
Mitochondrial injury plays an essential role in the pathogenesis of diabetic cardiomyopathy (DCM). Previous studies demonstrated that rosmarinic acid (RA) treatment prevented high glucose-induced mitochondrial injury in vitro. However, whether RA can ameliorate cardiac function by preventing mitochondrial injury in DCM is unknown. The SIRT1/PGC-1α pathway has emerged as an important regulator of metabolic control and other mitochondrial functions. The present study was undertaken to determine the effects of RA on mitochondrial and cardiac function in DCM as well as the involvement of the SIRT1/PGC-1α pathway. Our results revealed that RA improved cardiac systolic and diastolic function and prevented mitochondrial injury in DCM, as shown by the reduced blood glucose and lipid levels, increased mitochondrial membrane potential levels, improved adenosine triphosphate synthesis, and inhibited apoptosis (P < 0.05). Moreover, RA upregulated the expression of SIRT1 and PGC-1α in DCM mice and high glucose-treated H9c2 cardiomyocytes (P < 0.05). Further mechanistic studies in H9c2 cardiomyocytes revealed that suppression of SIRT1 by Sh-SIRT1 counteracted the effects of RA on high glucose-induced abnormal metabolism of glucose and lipids, oxidative stress and apoptosis (P < 0.05). Taken together, these data indicate that RA prevented mitochondrial injury and cardiac dysfunction in DCM mice, and the SIRT1/PGC-1α pathway mediated the protective effects of RA.
线粒体损伤在糖尿病心肌病（DCM）的发病机制中起着至关重要的作用。先前的研究表明迷迭香酸（RA）治疗可预防体外高葡萄糖诱导的线粒体损伤。然而，RA 是否可以通过预防 DCM 中的线粒体损伤来改善心脏功能尚不清楚。SIRT1/PGC-1α 途径已成为代谢控制和其他线粒体功能的重要调节剂。本研究旨在确定 RA 对 DCM 中线粒体和心脏功能的影响以及 SIRT1/PGC-1α 途径的参与。我们的结果表明，RA 改善了 DCM 的心脏收缩和舒张功能，并预防了线粒体损伤，表现为血糖和血脂水平降低，线粒体膜电位水平升高，三磷酸腺苷合成增加，以及抑制凋亡（P < 0.05）。此外，RA 上调了 DCM 小鼠和高葡萄糖处理的 H9c2 心肌细胞中 SIRT1 和 PGC-1α 的表达（P < 0.05）。在 H9c2 心肌细胞中的进一步机制研究表明，Sh-SIRT1 抑制 SIRT1 可拮抗 RA 对高葡萄糖诱导的葡萄糖和脂质异常代谢、氧化应激和凋亡的作用（P < 0.05）。综上所述，这些数据表明 RA 可预防 DCM 小鼠的线粒体损伤和心脏功能障碍，并且 SIRT1/PGC-1α 途径介导了 RA 的保护作用。
