Danshen and Zhizi Compatibility Alleviates Heart Injury and Cardiac Ferroptosis in Myocardial Infarction in Rats by Cyclic Adenosine Monophosphate/Protein Kinase A Signaling

The Heart Surgery Forum Pub Date : 2024-03-17 DOI:10.59958/hsf.7149

Jianqiao Zhao, Yifan Li, Hao Zhi, Wanying Hong, Jianping Shen

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Abstract

Objective: To investigate the effect and mechanism of the Danshen and Zhizi Compatibility (DZ) on alleviating heart injury and cardiac ferroptosis in rats with myocardial infarction. Methods: A rat model of myocardial infarction was established by ligation of the left anterior descending artery. The rats were equally and randomly divided into 5 groups. The sham group underwent open-chest surgery without arterial ligation, while the other 4 groups underwent surgery, including 3 groups treated with low dose (4 g/kg/d), high dose (8 g/kg/d) DZ and high dose (8 g/kg/d) DZ supplemented with H-89 (0.5 mg/kg/d) respectively. The sham and myocardial infarction group received the same volume of saline. 14 days after surgery, the serum and heart tissues were harvested to detect cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activity, heart injury and the level of ferroptosis. Results: G-protein coupled receptors (GPCRs) have a high binding affinity with the main components of DZ, which indicated that DZ probably contributed to ameliorating cardiac injury by activating downstream cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling. Treatment with the high dose of DZ significantly increased cAMP concentration in the serum, PKA activity in the heart tissue and upregulated perilipin (PLIN)5 expression. DZ significantly attenuated heart injury, whereas H-89 reversed the protective effects of DZ. In addition, DZ administration inhibited ferroptosis as evidenced by reduced malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) levels. In addition, DZ increased glutathione (GSH) levels and Glutathione peroxidase (GPX)4 protein expression in heart tissue, whereas H-89 abrogated the regulatory effect of DZ. Conclusion: Our results demonstrated that DZ alleviated heart injury and cardiac ferroptosis in myocardial infarction through the cAMP-PKA signalling pathway.

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丹参与枳实配伍通过单磷酸环磷酸腺苷/蛋白激酶 A 信号传导缓解心肌梗死大鼠的心脏损伤和心肌铁变态反应

目的探讨丹参与枳实配伍对减轻心肌梗死大鼠心脏损伤和心肌铁变态反应的作用及机制。研究方法通过结扎左前降支动脉建立心肌梗死大鼠模型。大鼠平均随机分为 5 组。假组进行开胸手术，不结扎动脉；其余 4 组进行手术，其中 3 组分别使用低剂量（4 g/kg/d）、高剂量（8 g/kg/d）DZ 和高剂量（8 g/kg/d）DZ 并辅以 H-89 （0.5 mg/kg/d）治疗。假组和心肌梗死组接受相同量的生理盐水。术后14天，采集血清和心脏组织，检测环磷酸腺苷（cAMP）和蛋白激酶A（PKA）活性、心脏损伤和铁蛋白沉积水平。结果G-蛋白偶联受体（GPCR）与DZ的主要成分有很高的结合亲和力，这表明DZ可能通过激活下游环磷酸腺苷（cAMP）/蛋白激酶A（PKA）信号转导来改善心脏损伤。大剂量DZ能显著增加血清中的cAMP浓度和心脏组织中的PKA活性，并上调过脂素（PLIN）5的表达。DZ能明显减轻心脏损伤，而H-89能逆转DZ的保护作用。此外，DZ还能抑制铁变态反应，这体现在丙二醛（MDA）和4-羟基壬烯醛（4-HNE）水平的降低。此外，DZ 增加了心脏组织中谷胱甘肽（GSH）的水平和谷胱甘肽过氧化物酶（GPX）4 蛋白的表达，而 H-89 则削弱了 DZ 的调节作用。结论我们的研究结果表明，DZ 可通过 cAMP-PKA 信号通路减轻心肌梗死的心脏损伤和心脏铁蛋白沉积。

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The Heart Surgery Forum

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