The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China; Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, Hubei, China.
Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, Hubei, China; College of Medicine and Health Sciences, China Three Gorges University, Yichang, Hubei, China.
Exp Gerontol. 2023 Oct 15;182:112305. doi: 10.1016/j.exger.2023.112305. Epub 2023 Oct 11.
Heart disease is a significant health concern for elderly individuals, with heart aging being the primary cause. Recent studies have shown that autophagy can play a protective role in preventing cardiac aging. Our previous research confirmed that Chikusetsu saponin IVa, a fundamental component of Saponins of Panax japonics (SPJ), can enhance basic autophagy levels in cardiomyocyte of isoproterenol induced cardiac fibrosis mice. However, it remains unclear whether SPJ possesses a protective effect on cardiac dysfunction during the natural aging process. Rats were randomly divided into four groups: adult control group (6 months old), aging group (24 months old), aging group treated with 10 mg/kg SPJ, and aging group treated with 30 mg/kg SPJ. The heart function, blood pressure, and heart mass index (HMI) were measured. Hematoxylin and eosin staining (H&E) and Wheat Germ Agglutinin (WGA) staining were used to observe the changes in morphology, while Masson staining was used to examine collagen deposition in the rat hearts and CD45 immunohistochemistry was conducted to examine the macrophage infiltration in heart tissues. TUNEL kit was used to detect apoptosis level of cardiomyocyte, and western blot was used to evaluate autophagy-related proteins as well as AMPK/mTOR/ULK1 pathway-related markers. SPJ treatment improved the cardiac function, reduced HMI, attenuated myocardial fiber disorder, inhibited inflammatory cell infiltration, and decreased collagen deposition and cardiomyocyte apoptosis in aging rats. Additionally, SPJ treatment decreased the expression of aging-related proteins and restored the expression of autophagy-related markers. SPJ activated autophagy through the activation of AMPK, which in turn increased the phosphorylation of ULK1(Ser555), while inhibited the phosphorylation of mTOR and ULK1(Ser757). Our study demonstrates that SPJ improves the cardiac function of aging rats by enhancing basal autophagy through the AMPK/mTOR/ULK1 pathway. These results offer a theoretical foundation and empirical evidence to support the clinical advancement of SPJ in enhancing age-related cardiac dysfunction.
心脏病是老年人的一个重大健康问题，心脏衰老是主要原因。最近的研究表明，自噬可以在预防心脏衰老方面发挥保护作用。我们之前的研究证实，齐墩果酸 IVa，是人参皂苷（SPJ）的基本成分，可以提高异丙肾上腺素诱导的心肌纤维化小鼠心肌细胞的基础自噬水平。然而，SPJ 是否对自然衰老过程中心脏功能障碍具有保护作用仍不清楚。大鼠随机分为四组：成年对照组（6 个月龄）、衰老组（24 个月龄）、衰老组给予 10mg/kg SPJ 治疗组和衰老组给予 30mg/kg SPJ 治疗组。测量心功能、血压和心脏质量指数（HMI）。苏木精和伊红染色（H&E）和麦胚凝集素（WGA）染色观察形态变化，马松染色观察大鼠心脏胶原沉积，CD45 免疫组化观察心脏组织中巨噬细胞浸润。TUNEL 试剂盒检测心肌细胞凋亡水平，Western blot 检测自噬相关蛋白及 AMPK/mTOR/ULK1 通路相关标志物。SPJ 治疗改善了心脏功能，降低了 HMI，减轻了心肌纤维紊乱，抑制了炎症细胞浸润，减少了胶原沉积和心肌细胞凋亡衰老大鼠。此外，SPJ 治疗降低了衰老相关蛋白的表达，恢复了自噬相关标志物的表达。SPJ 通过激活 AMPK 激活自噬，从而增加 ULK1（Ser555）的磷酸化，同时抑制 mTOR 和 ULK1（Ser757）的磷酸化。本研究表明，SPJ 通过 AMPK/mTOR/ULK1 通路增强基础自噬来改善衰老大鼠的心脏功能。这些结果为 SPJ 通过增强与年龄相关的心脏功能障碍的临床进展提供了理论基础和经验证据。
