title: Effects of aspirin on the ERK and PI3K/Akt signaling pathways in rats with acute pulmonary embolism.
abstract: 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.
authors.affiliation: Department of Intensive Care Unit, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Lingcong
authors.initials: L
authors.lastname: Wang
authors.forename: Jiannong
authors.initials: J
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yihui
authors.initials: Y
authors.lastname: Zhi
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Wu
authors.forename: Ronglin
authors.initials: R
authors.lastname: Jiang
authors.forename: Ruhui
authors.initials: R
authors.lastname: Yang
mesh_terms: D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020107:Troponin T / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D020107:Troponin T; C036309:fibrin fragment D; C495963:natriuretic peptide precursor type B, rat; D020097:Natriuretic Peptide, Brain; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D001241:Aspirin