Department of Geriatrics, Renmin Hospital of Wuhan University, Hubei, People's Republic of China.
Drug Des Devel Ther. 2020 Dec 18;14:5575-5587. doi: 10.2147/DDDT.S276972. eCollection 2020.
In this study, we investigated the protective effects and mechanism of action of echinacoside (ECH) from cistanche tubulosa extract in cardiomyocytes of diabetic mice.
Twenty healthy male mice aged 8 weeks were randomly divided into +ECH (n=10, ECH, 300 mg/(kg/d)), (n=10, saline), and control groups (n=9). Mice were monitored weekly for diet and activity. Mice were injected with 2% of pentobarbital sodium in week 10 and executed. Weight and free blood glucose (FBG) were measured weekly. Echocardiographs were used to detect cardiac function. HE staining, Sudan II staining, Masson's trichrome staining and Tunel assays were used to evaluate myocardial tissue pathological changes, collagen fiber deposition, lipid accumulation and apoptosis rates in cardiomyocytes, respectively. Western blot and RT-PCR analysis were used to detect the expression of components of the PPAR-α/M-CPT-1 and p53/p38MAPK signaling axis.
Compared to mice, ECH groups showed lower blood glucose and lipid levels. Deterioration in cardiac function was also delayed following ECH treatment. Histopathological analysis showed that ECH significantly improved myocardial tissue in mice, including reduced intercellular spaces, regular arrangements, improved extracellular matrix deposition, and reduced lipid accumulation. ECH also significantly reduced oxidative stress levels in myocardial tissue in mice. Moreover, ECH inhibited PPAR-α/M-CPT-1 signaling, downregulated CD36, and upregulated glucose transporter type 4 (GLUT-4) expression in mouse models of DCM. ECH also inhibited p53/p38MAPK signaling, downregulated caspase-3 and caspase-8, and upregulated Bcl-2/Bax in mouse models of DCM.
ECH displays protective effects in DCM, including the inhibition of cardiac apoptosis and oxidative stress, and improved lipid metabolism in cardiomyocytes. ECH also inhibits cardiac apoptosis through its regulation of p53/p38MAPK signaling, and prevents lipid accumulation through suppression of the PPAR-α/M-CPT-1 signaling axis.
本研究旨在探讨肉苁蓉提取物中的松果菊苷（ECH）对糖尿病小鼠心肌细胞的保护作用及其作用机制。
将 20 只 8 周龄健康雄性小鼠随机分为+ECH 组（n=10，ECH，300mg/（kg/d））、模型组（n=10，生理盐水）和对照组（n=9）。每周监测饮食和活动情况。第 10 周时，所有小鼠均被注射 2%戊巴比妥钠并处死。每周测量体重和空腹血糖（FBG）。使用超声心动图检测心功能。HE 染色、苏丹 II 染色、Masson 三色染色和 Tunel 检测分别用于评估心肌组织病理学变化、胶原纤维沉积、心肌细胞内脂质积累和细胞凋亡率。Western blot 和 RT-PCR 分析用于检测过氧化物酶体增殖物激活受体-α/肉碱棕榈酰转移酶-1（PPAR-α/M-CPT-1）和 p53/p38MAPK 信号通路相关成分的表达。
与模型组相比，ECH 组血糖和血脂水平较低，心脏功能恶化延迟。ECH 明显改善了模型小鼠的心肌组织，包括减少细胞间隙、排列规则、改善细胞外基质沉积和减少脂质积累。ECH 还显著降低了模型小鼠心肌组织中的氧化应激水平。此外，ECH 抑制了 DCM 模型小鼠的 PPAR-α/M-CPT-1 信号通路，下调了 CD36 表达，上调了葡萄糖转运蛋白 4（GLUT-4）表达。ECH 还抑制了 DCM 模型小鼠的 p53/p38MAPK 信号通路，下调了半胱氨酸天冬氨酸蛋白酶-3 和半胱氨酸天冬氨酸蛋白酶-8 的表达，上调了 B 细胞淋巴瘤/白血病-2（Bcl-2）/Bcl-2 相关 X 蛋白（Bax）的表达。
ECH 对 DCM 具有保护作用，包括抑制心肌细胞凋亡和氧化应激，改善心肌细胞脂质代谢。ECH 通过调节 p53/p38MAPK 信号通路抑制心脏细胞凋亡，通过抑制过氧化物酶体增殖物激活受体-α/肉碱棕榈酰转移酶-1 信号轴防止脂质积累。
