Zhang Shenjie, Ye Ying, Li Qi, Zhao Juan, Song Rongrong, Huang Chao, Lu Xu, Huang Chen, Yin Le, You Qingsheng
Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
Department of Ultrasound, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
Inflammation. 2024 Nov 25. doi: 10.1007/s10753-024-02193-1.
Andrographolide (AGP), a bioactive diterpene lactone, is an active constituent extracted from Andrographis paniculata. It has many biological activities, such as antioxidant, antitumor, antivirus, anti-inflammation, hepatoprotection, and cardioprotection. The aim of the present study is to investigate the cardioprotective effects of AGP in a mouse model of myocardial ischemia-reperfusion injury (MIRI). Adult male C57BL/6 J mice were pre-treated orally with AGP (25 mg/kg) for six days. After 30 min of the left anterior descending coronary artery occlusion followed by 24 h of reperfusion, mice received an additional dose of AGP. The results showed that: (i) AGP pretreatment significantly reduced myocardial infarct size and cardiac injury biomarkers in MIRI mice and improved left ventricular ejection fraction (EF) and fractional shortening (FS); (ii) AGP pretreatment attenuated MIRI-induced oxidative stress imbalance in MIRI mice by increasing total antioxidant capacity (T-AOC) and reducing the levels of hydrogen peroxide (HO), nitric oxide (NO), malondialdehyde (MDA), and dihydroethidium (DHE); (iii) AGP pretreatment increased Bcl-2 expression and decreased caspase-3 and Bax expression in ischemic myocardial tissue, along with a reduction in TUNEL-positive cells. Further analysis showed that stimulation by I/R decreased peroxisome proliferator-activated receptor-α (PPAR-α) expression in ischemic cardiac tissue, which was prevented by AGP administration. Moreover, administration of the PPAR-α antagonist GW6471 (1 mg/kg) abolished the protective effect of AGP on oxidative stress and apoptosis in the ischemic heart tissue of mice stimulated by ischemia-reperfusion. Taken together, these results suggest that AGP attenuates MIRI-induced cardiac injury by up-regulating PPAR-α expression, thereby preventing oxidative stress and cellular apoptosis.
穿心莲内酯（AGP）是一种具有生物活性的二萜内酯，是从穿心莲中提取的活性成分。它具有许多生物学活性，如抗氧化、抗肿瘤、抗病毒、抗炎、保肝和心脏保护作用。本研究的目的是探讨AGP在小鼠心肌缺血再灌注损伤（MIRI）模型中的心脏保护作用。成年雄性C57BL/6 J小鼠口服AGP（25 mg/kg）预处理6天。在左冠状动脉前降支闭塞30分钟后再灌注24小时，小鼠再接受一剂AGP。结果表明：（i）AGP预处理显著减小了MIRI小鼠的心肌梗死面积，降低了心脏损伤生物标志物水平，并改善了左心室射血分数（EF）和缩短分数（FS）；（ii）AGP预处理通过增加总抗氧化能力（T-AOC），降低过氧化氢（HO）、一氧化氮（NO）、丙二醛（MDA）和二氢乙锭（DHE）水平，减轻了MIRI小鼠MIRI诱导的氧化应激失衡；（iii）AGP预处理增加了缺血心肌组织中Bcl-2的表达，降低了caspase-3和Bax的表达，同时TUNEL阳性细胞减少。进一步分析表明，I/R刺激降低了缺血心脏组织中过氧化物酶体增殖物激活受体-α（PPAR-α）的表达，而AGP给药可预防这种降低。此外，给予PPAR-α拮抗剂GW6471（1 mg/kg）可消除AGP对缺血再灌注刺激的小鼠缺血心脏组织氧化应激和细胞凋亡的保护作用。综上所述，这些结果表明AGP通过上调PPAR-α表达减轻MIRI诱导的心脏损伤，从而预防氧化应激和细胞凋亡。
