Abstract：
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.
摘要：
心脏病是老年人的重大健康问题，心脏老化是主要原因。最近的研究表明，自噬可以在预防心脏老化方面发挥保护作用。我们先前的研究证实了Chikusetsu皂苷IVa，人参皂苷（SPJ）的基本成分，能增强异丙肾上腺素诱导的心肌纤维化小鼠心肌细胞碱性自噬水平。然而,目前尚不清楚SPJ在自然衰老过程中是否对心脏功能障碍具有保护作用。大鼠随机分为4组:成年对照组(6月龄),老年组（24个月大），衰老组给予10mg/kgSPJ，衰老组用30mg/kgSPJ治疗。心脏功能,血压,测量心脏质量指数(HMI)。苏木素和伊红染色(H&E)和小麦胚芽凝集素(WGA)染色观察形态学变化,同时采用Masson染色法检测大鼠心脏胶原沉积情况,采用CD45免疫组化法检测心脏组织巨噬细胞浸润情况。用TUNEL试剂盒检测心肌细胞凋亡水平,免疫印迹用于评估自噬相关蛋白以及AMPK/mTOR/ULK1通路相关标志物。SPJ治疗改善心功能，减少HMI，减轻心肌纤维紊乱，抑制炎症细胞浸润，衰老大鼠胶原沉积和心肌细胞凋亡减少。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,这反过来又增加了ULK1（Ser555）的磷酸化，同时抑制mTOR和ULK1(Ser757)的磷酸化。我们的研究表明，SPJ通过AMPK/mTOR/ULK1通路增强基础自噬，从而改善衰老大鼠的心功能。这些结果提供了理论基础和经验证据，以支持SPJ在增强与年龄相关的心脏功能障碍方面的临床进展。
