Chen Rui, Chen Hongjian, Yang Zijiang, Zhu Liyun, Bei Yihua, Chen Wei, Qiu Yan
Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.
Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China.
Heliyon. 2023 Mar 11;9(3):e14479. doi: 10.1016/j.heliyon.2023.e14479. eCollection 2023 Mar.
Diabetic cardiomyopathy (DCM) is highly prevalent and increases the risk of heart failure and sudden death. Therefore, proper and effective treatments for DCM are in urgent demand. Danlou tablet (Dan) is reported to confer protective effects on several heart diseases. However, to our knowledge, whether Dan provides protection against DCM is unclear. In this study, we explored the effect of Dan on DCM with the DCM model using AC16 cardiomyocytes. We found that Dan treatment significantly reduced cardiomyocyte apoptosis and oxidative stress in high-glucose (HG)-treated cardiomyocytes, as evidenced by decreased Annexin V-FITC+ cardiomyocytes, intracellular reactive oxygen species (ROS) levels, Bax/Bcl2 ratio, and cleaved-Caspase3/Caspase3 ratio. Interestingly, Dan treatment caused a decreased level of microRNA-34a (miR-34a), which could enhance cardiomyocyte apoptosis. Furthermore, miR-34a mimic blocked Dan's effect in apoptosis prevention. Finally, we observed that the miR-34a mimic effectively decreased the level of sirtuin 1 (SIRT1), while the miR-34a inhibitor increased the level of SIRT1. And downregulation of SIRT1 effectively reversed the effect of miR-34a inhibitor on cardiomyocyte apoptosis. Taken together, our study showed that Dan prevented HG-induced cardiomyocyte apoptosis through downregulating miR-34a and upregulating SIRT1. Our study has provided experimental support for the potential use of Dan in treating DCM. Further detailed study of Dan and the underlying mechanisms may shed light on the prevention and treatment of DCM.
糖尿病性心肌病（DCM）非常普遍，会增加心力衰竭和猝死的风险。因此，迫切需要针对DCM的恰当且有效的治疗方法。据报道，丹蒌片（Dan）对多种心脏病具有保护作用。然而，据我们所知，Dan是否能预防DCM尚不清楚。在本研究中，我们使用AC16心肌细胞建立DCM模型，探讨了Dan对DCM的影响。我们发现，Dan处理显著降低了高糖（HG）处理的心肌细胞中的心肌细胞凋亡和氧化应激，这可通过膜联蛋白V-FITC+心肌细胞减少、细胞内活性氧（ROS）水平、Bax/Bcl2比值以及裂解的Caspase3/Caspase3比值降低来证明。有趣的是，Dan处理导致微小RNA-34a（miR-34a）水平降低，而miR-34a可增强心肌细胞凋亡。此外，miR-34a模拟物阻断了Dan在预防凋亡方面的作用。最后，我们观察到miR-34a模拟物有效降低了沉默调节蛋白1（SIRT1）的水平，而miR-34a抑制剂则提高了SIRT1的水平。并且SIRT1的下调有效逆转了miR-34a抑制剂对心肌细胞凋亡的影响。综上所述，我们的研究表明，Dan通过下调miR-34a和上调SIRT1来预防HG诱导的心肌细胞凋亡。我们的研究为Dan在治疗DCM方面的潜在应用提供了实验支持。对Dan及其潜在机制的进一步详细研究可能会为DCM的预防和治疗提供线索。
