Zhang Mingming, Wang Shanjie, Cheng Zheng, Xiong Zhenyu, Lv Jianjun, Yang Zhi, Li Tian, Jiang Shuai, Gu Jing, Sun Dongdong, Fan Yanhong
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Biochem Biophys Res Commun. 2017 Nov 25;493(3):1280-1287. doi: 10.1016/j.bbrc.2017.09.151. Epub 2017 Sep 28.
Diabetic cardiomyopathy is identified as cardiac ventricular dysfunction induced by an insulin shortage in diabetic patients. Our previous studies have shown that Polydatin (PD) alleviates cardiac dysfunction after myocardial infarction (MI) injury. Nevertheless, the mechanism by which PD regulates diabetic cardiomyopathy has not been reported.
In this study, we demonstrated the effects and described the mechanisms of PD in diabetic cardiomyopathy in both adult mouse hearts and neonatal mouse cardiomyocytes. We injected streptozotocin (STZ) to induce the DM model in wild-type (WT) and Sirt3 knockout (Sirt3) mice. Mitochondrial bioenergetics in diabetic mice were detected by measuring citrate synthase activity and ATP content. The extent of autophagy regulation by PD was investigated by detecting the levels of Beclin 1, Atg5, LC3 and p62.
Compared to the WT mouse hearts, hearts from the diabetic mice exhibited better cardiac function and a higher level of autophagy. Moreover, mitochondrial function in the diabetic mouse hearts was improved after PD treatment. However, PD treatment had no effect on the Sirt3 knockout diabetic mouse hearts. Additionally, PD increased autophagy flux in the cardiomyocytes that were cultured in high-glucose medium for 48 h. In addition, PD had no effects on the cardiomyocytes under high-glucose conditions when we down-regulated Sirt3.
Altogether, PD attenuated cardiac dysfunction, increased autophagy flux and improved mitochondrial bioenergetics by up-regulating Sirt3 in the diabetic mice.
糖尿病性心肌病被认为是糖尿病患者胰岛素缺乏引起的心室功能障碍。我们之前的研究表明，白藜芦醇苷（PD）可减轻心肌梗死（MI）损伤后的心脏功能障碍。然而，PD调节糖尿病性心肌病的机制尚未见报道。
在本研究中，我们在成年小鼠心脏和新生小鼠心肌细胞中证实了PD对糖尿病性心肌病的作用并描述了其机制。我们注射链脲佐菌素（STZ）以在野生型（WT）和沉默信息调节因子3基因敲除（Sirt3）小鼠中诱导糖尿病模型。通过测量柠檬酸合酶活性和ATP含量来检测糖尿病小鼠的线粒体生物能量学。通过检测Beclin 1、Atg5、LC3和p62的水平来研究PD对自噬调节的程度。
与WT小鼠心脏相比，糖尿病小鼠的心脏表现出更好的心脏功能和更高水平的自噬。此外，PD治疗后糖尿病小鼠心脏的线粒体功能得到改善。然而，PD治疗对Sirt3基因敲除的糖尿病小鼠心脏没有影响。此外，PD增加了在高糖培养基中培养48小时的心肌细胞中的自噬通量。此外，当我们下调Sirt3时，PD在高糖条件下对心肌细胞没有影响。
总之，PD通过上调糖尿病小鼠中的Sirt3减轻心脏功能障碍，增加自噬通量并改善线粒体生物能量学。
