Wu Wanqi, Wang Jun, Wang Guanglu, Wang Feibiao, Yang Yue, Liu Zhijun, Song Qimei, Chen Si, Chen Huizhen
Institute of Neuroscience, The First Affiliated Hospital of Kangda College of Nanjing Medical University, The Affiliated Lianyungang Hospital of Xuzhou Medical University (The First People's Hospital of Lianyungang), Lianyungang, 222000, China.
School of Basic Medical Sciences, Kangda College of Nanjing Medical University, Lianyungang, 222000, China.
Mol Biol Rep. 2025 Mar 20;52(1):329. doi: 10.1007/s11033-025-10421-6.
Sepsis can cause severe cardiac damage, and matrix metalloproteinase 9 (MMP9) is involved in the inflammatory response and tissue injury processes. Monotropein is a monoterpene glycoside with anti-inflammatory and antioxidant effects. This study aims to investigate whether monotropein can alleviate sepsis-induced cardiac injury by affecting the activity of MMP9.
The correlation between MMP9 and septic cardiac injury was explored using differential expression gene analysis from the GEO database and an in vitro lipopolysaccharide (LPS)-stimulated H9c2 cell model. In a cecal ligation and puncture (CLP)-induced mouse sepsis model, the effects of monotropein on myocardial cell apoptosis, inflammatory factor expression, and antioxidant enzyme levels were validated through drug administration. The results showed that MMP9 was significantly upregulated in sepsis patients. In the H9c2 cell model, LPS-induced MMP9 activity was positively correlated with cell damage. Inhibition of MMP9 alleviates LPS-induced myocardial matrix disruption and apoptosis. Monotropein exerts anti-matrix degradation and anti-apoptotic effects through MMP9 in LPS-induced H9c2 cells. Monotropein also reduced the expression of LPS-induced inflammatory factors (TNF-α, IL-1β, IL-6).In the mouse model, monotropein decreased oxidative stress damage (lower MDA levels, increased GSH, T-AOC, CAT enzyme activity), and improved cardiac injury by inhibiting myocardial cell apoptosis-related proteins (Bax, Bcl-2, and Caspase-3 activation).
Monotropein exerts a protective effect on septic cardiac injury by inhibiting MMP9 activity, reducing inflammatory response, and enhancing antioxidant capacity, thereby ameliorating myocardial cell damage and apoptosis.
脓毒症可导致严重的心脏损伤，基质金属蛋白酶9（MMP9）参与炎症反应和组织损伤过程。水晶兰苷是一种具有抗炎和抗氧化作用的单萜糖苷。本研究旨在探讨水晶兰苷是否能通过影响MMP9的活性来减轻脓毒症诱导的心脏损伤。
利用GEO数据库的差异表达基因分析和体外脂多糖（LPS）刺激的H9c2细胞模型，探讨MMP9与脓毒症性心脏损伤之间的相关性。在盲肠结扎和穿刺（CLP）诱导的小鼠脓毒症模型中，通过给药验证了水晶兰苷对心肌细胞凋亡、炎症因子表达和抗氧化酶水平的影响。结果显示，脓毒症患者的MMP9显著上调。在H9c2细胞模型中，LPS诱导的MMP9活性与细胞损伤呈正相关。抑制MMP9可减轻LPS诱导的心肌基质破坏和凋亡。水晶兰苷在LPS诱导的H9c2细胞中通过MMP9发挥抗基质降解和抗凋亡作用。水晶兰苷还降低了LPS诱导的炎症因子（TNF-α、IL-1β、IL-6）的表达。在小鼠模型中，水晶兰苷降低了氧化应激损伤（降低MDA水平, 增加GSH、T-AOC、CAT酶活性），并通过抑制心肌细胞凋亡相关蛋白（Bax、Bcl-2和Caspase-3激活）改善了心脏损伤。
水晶兰苷通过抑制MMP9活性、减轻炎症反应和增强抗氧化能力，对脓毒症性心脏损伤发挥保护作用, 从而改善心肌细胞损伤和凋亡。
