Department of Intensive Care Unit, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Mol Med Rep. 2013 Nov;8(5):1465-71. doi: 10.3892/mmr.2013.1676. Epub 2013 Sep 10.
Inflammation contributes to acute pulmonary embolism (APE). However, the contributions of the extracellular signal‑regulated protein kinases (ERK) and phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signaling pathways have not yet been elucidated. The aim of this study was to examine the effects of aspirin on ERK and PI3K/Akt signaling in a rat model of APE and evaluate the prognostic values of brain natriuretic peptide (BNP), troponin (TnT) and D‑Dimer. A total of 108 Sprague‑Dawley rats were assigned into the control, sham, model and low‑, medium‑ and high‑dose aspirin (150, 300 and 600 mg/kg, respectively) groups. In each group, six rats were sacrificed 6, 24 and 72 h subsequent to the induction of APE to collect the lungs and serum. Western blot analysis was used to assess ERK, PI3K and Akt expression; enzyme‑linked immunosorbent assay (ELISA) was used to analyze BNP, TnT and D‑Dimer levels; and changes in lung pathology were evaluated using hematoxylin and eosin (H&E) staining. The results showed that ERK and PI3K levels were decreased in the control, sham and the three aspirin groups at all time‑points compared with the model group (P<0.01). The exception was in the medium‑dose aspirin group at 24 h. The serum levels of BNP, TnT and D‑Dimer were lower in the control and sham groups at all time‑points compared with the model group (P<0.05). Furthermore, the levels of BNP, TnT and D‑Dimer levels were decreased in the aspirin‑treated groups (P<0.05) and markedly increased in the model group (P<0.05) at 24 h compared with the levels at 6 h. Pulmonary embolism, alveolar wall necrosis and hemorrhage were observed in the model group 6, 24 and 72 h subsequent to the induction of the model. However, congestion and inflammation were attenuated following aspirin treatment. In conclusion, aspirin reduces lung damage and improves prognosis. Decreased ERK, PI3K and Akt expression in the lungs and reduced levels of BNP, TnT and D‑Dimer may be important factors in the effects observed.
炎症导致急性肺栓塞（APE）。然而，细胞外信号调节蛋白激酶（ERK）和磷酸肌醇 3 激酶/蛋白激酶 B（PI3K/Akt）信号通路的贡献尚未阐明。本研究旨在研究阿司匹林对 APE 大鼠模型中 ERK 和 PI3K/Akt 信号的影响，并评估脑钠肽（BNP）、肌钙蛋白（TnT）和 D-二聚体的预后价值。共将 108 只 Sprague-Dawley 大鼠分为对照组、假手术组、模型组以及低、中、高剂量阿司匹林（分别为 150、300 和 600mg/kg）组。在每组中，6 只大鼠在诱导 APE 后 6、24 和 72 小时处死，收集肺和血清。Western blot 分析用于评估 ERK、PI3K 和 Akt 表达；酶联免疫吸附测定（ELISA）用于分析 BNP、TnT 和 D-二聚体水平；苏木精和伊红（H&E）染色评估肺病理变化。结果显示，与模型组相比，对照组、假手术组和三个阿司匹林组在所有时间点的 ERK 和 PI3K 水平均降低（P<0.01）。但在中剂量阿司匹林组中，24 小时时除外。在所有时间点，对照组和假手术组的 BNP、TnT 和 D-二聚体血清水平均低于模型组（P<0.05）。此外，阿司匹林治疗组的 BNP、TnT 和 D-二聚体水平降低（P<0.05），与 6 小时相比，模型组在 24 小时时明显升高（P<0.05）。在模型诱导后 6、24 和 72 小时，模型组观察到肺栓塞、肺泡壁坏死和出血。然而，阿司匹林治疗后，充血和炎症得到缓解。总之，阿司匹林可减轻肺损伤并改善预后。肺组织中 ERK、PI3K 和 Akt 表达降低以及 BNP、TnT 和 D-二聚体水平降低可能是观察到的作用的重要因素。
