【摘要】 目的 探讨TSDP对衰老心肌细胞舒张功能障碍的作用及分子机制。方法 采用AGEs诱导乳大鼠原代心肌细胞建立衰老模型，将其分为对照组、AGEs组、TSDP组。通过慢病毒转染过表达SIRT3验证其关键作用。检测指标：细胞静息张力以及SIRT3、FoxO3a、SERCA2a mRNA表达；Seahorse检测OCR和ATP。结果 TSDP降低衰老心肌细胞静息张力，恢复OCR、ATP产量，上调SIRT3表达，降低FoxO3a水平，恢复SERCA2a表达(P<0.01);SIRT3过表达则增强TSDP的保护作用(P<0.01)。结论 TSDP通过激活SIRT3-FoxO3a信号轴，改善线粒体功能，减轻心肌细胞舒张功能障碍，为HFpEF的治疗提供新靶点。更多还原

【Abstract】 Objective To investigate the effect of TSDP on diastolic dysfunction in aging cardiomyocytes and its molecular mechanism.Methods An aging model was established in primary neonatal rat cardiomyocytes induced by advanced glycation end products(AGEs). The cells were divided into control, AGEs, and TSDP groups. The key role of SIRT3 was verified via lentiviral-mediated overexpression. The following parameters were measured: resting tension of cardiomyocytes, mRNA expression levels of SIRT3, FoxO3a, and SERCA2a, as well as OCR and ATP production using Seahorse analysis. Results TSDP reduced resting tension in aging cardiomyocytes, restored OCR and ATP production, upregulated SIRT3 expression, reduced FoxO3a levels, and restored SERCA2a expression(P<0.01). Overexpression of SIRT3 enhanced the protective effects of TSDP(P<0.01).Conclusion TSDP improves mitochondrial function and alleviates diastolic dysfunction in cardiomyocytes by activating the SIRT3-FoxO3a signaling axis, thereby providing a novel therapeutic target for heart failure with preserved ejection fraction(HFpEF).更多还原