Department of Cardiovascular Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China.
Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, China.
Immunopharmacol Immunotoxicol. 2024 Dec;46(6):893-901. doi: 10.1080/08923973.2024.2412113. Epub 2024 Oct 29.
This study examines the therapeutic potential of monotropein (Mon) in a rat model of acute pulmonary embolism (APE), aiming to elucidate its mechanistic role and provide new insights for APE treatment.
Thirty Sprague Dawley (SD) rats were randomly assigned to five groups ( = 6 per group): sham, Mon (40 mg/kg), APE, APE + 20 mg/kg Mon, and APE + 40 mg/kg Mon. APE was induced autologous thrombus infusion in all groups except sham and Mon-only groups. We assessed blood gas parameters, lung wet/dry weight (W/D) ratio, and oxidative stress markers. Additionally, excised lung tissues underwent evaluation for serum inflammatory factors ELISA, apoptotic cells TUNEL assay, and protein expression Western blot.
Compared to the sham group, APE-induced rats exhibited significantly elevated blood oxygen levels and increased pro-inflammatory factors, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8. Mon treatment effectively mitigated these APE-induced changes, reducing blood oxygen concentration and downregulating IL-1β and TNF-α levels. Furthermore, Mon demonstrated anti-apoptotic effects by decreasing cleaved caspase-3 and Bax protein levels while upregulating Bcl-2 expression. Mon also suppressed nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation levels of p65/RelA and IκBα proteins, while the total protein level of IκBα was increased with Mon treatment.
Mon effectively ameliorated lung tissue injury in APE rats by inhibiting apoptosis, attenuating inflammatory responses, and alleviating oxidative stress. These beneficial effects appear to be mediated through modulation of the NF-κB pathway, suggesting Mon as a promising therapeutic candidate for APE treatment.
本研究旨在探讨莫诺苯宗（Mon）在急性肺栓塞（APE）大鼠模型中的治疗潜力，旨在阐明其作用机制，并为 APE 的治疗提供新的见解。
30 只 Sprague Dawley（SD）大鼠随机分为五组（每组 n=6）：假手术组、Mon（40mg/kg）组、APE 组、APE+20mg/kg Mon 组和 APE+40mg/kg Mon 组。除假手术组和 Mon 组外，所有组均通过自体血栓输注诱导 APE。我们评估了血气参数、肺湿/干重（W/D）比和氧化应激标志物。此外，还通过 ELISA 评估了肺组织中血清炎症因子、TUNEL 法评估了凋亡细胞、Western blot 评估了蛋白表达。
与假手术组相比，APE 诱导的大鼠表现出明显的血氧水平升高和促炎因子（包括白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α和 IL-8）的增加。Mon 治疗可有效减轻这些 APE 诱导的变化，降低血氧浓度并下调 IL-1β和 TNF-α水平。此外，Mon 通过降低裂解的 caspase-3 和 Bax 蛋白水平并上调 Bcl-2 表达表现出抗凋亡作用。Mon 还通过抑制 p65/RelA 和 IκBα 蛋白的磷酸化水平来抑制核因子-κB（NF-κB）的激活，同时 Mon 治疗还增加了 IκBα 的总蛋白水平。
Mon 通过抑制凋亡、减轻炎症反应和缓解氧化应激，有效改善 APE 大鼠的肺组织损伤。这些有益作用似乎是通过调节 NF-κB 通路介导的，提示 Mon 可能是 APE 治疗的有希望的治疗候选物。
