Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model
Animal model study published in PeerJ (2024)
Abstract
BACKGROUND: Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. METHODS: Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. RESULTS: R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. CONCLUSION: R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Recombinant hirudin (0.25, 0.5, 1.0 mg/kg subcutaneously) significantly reduced mean pulmonary artery pressure, right ventricular pressure, oxidative stress markers (MDA, H2O2, MPO), and inflammatory mediators (ET-1, TXB2, ERK1/2, P65) in a rat model of acute pulmonary embolism.
Why This Matters for Hirudotherapy
This study investigated the effects of subcutaneous recombinant hirudin (R-hirudin) at three dose levels (0.25, 0.5, and 1.0 mg/kg) in a Sprague-Dawley rat model of acute pulmonary embolism (APE). R-hirudin significantly reduced pulmonary artery pressures, improved oxygenation, decreased oxidative stress markers (MDA, H2O2, MPO), lowered pro-thrombotic mediators (ET-1, TXB2), and attenuated histopathological lung injury and apoptosis in lung tissues. The findings are relevant to understanding the pharmacological effects of recombinant hirudin in a thrombotic disease model. However, this is an animal study with no human data, and findings cannot be directly extrapolated to clinical management. The abstract does not describe R-hirudin as leech-derived.
Citation
Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model.
Wei X et al. · PeerJ, 2024
Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026