Hirudin ameliorates myocardial ischemia-reperfusion injury in a rat model of hemorrhagic shock and resuscitation: roles of NLRP3-signaling pathway
Basic science / preclinical published in Mol Cell Biochem (2023)
Abstract
Severe hemorrhage shock and resuscitation (HSR) has been reported to induce myocardial ischemia-reperfusion injury (MIRI), resulting in a poor prognosis. Hirudin, an effective thrombin inhibitor, can offer protection against MIRI. This study aimed to determine if hirudin administration ameliorates HSR-induced MIRI and the underlying mechanism. A rat model of HSR was established by bleeding rats to a mean arterial blood pressure of 30-35 mmHg for 45 min and then resuscitating them with all the shed blood through the left femoral vein. After HSR, 1 mg/kg of hirudin was administrated immediately. At 24 h after HSR, the cardiac injury was assessed using serum CK-MB, cTnT, hematoxylin-eosin (HE) staining, echocardiography, M1-polarized macrophages, and pyroptosis-associated factors, including cleaved caspase-1, Gasdermin D (GSDMD) N-terminal, IL-1β, and IL-18 were measured by immunofluorescence and western blot assays. Nigericin, a unique agonist, was utilized to evaluate the responsibilities of NLRP3 signaling. Under the HSR condition, rats exhibited a significant increase in myocardial injury score, an elevation of serum cTnT, CK-MB levels, an aggrandization of M1-polarized macrophages, an upregulation of pyroptosis-associated factors, including cleaved caspase-1, GSDMD N-terminal, IL-1β, and IL-18, but a significant decrease in left ventricular ejection fraction (EF%) and a reduction of left ventricular fractional shortening (FS%), while hirudin administration partially restored the changes. However, the NLRP3 agonist nigericin reversed the cardioprotective effects of hirudin. We determined the cardioprotective effects of hirudin against HSR-induced MIRI. The mechanism may involve the inhibition of NLRP3-induced pyroptosis.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Rat model of hemorrhagic shock + resuscitation shows hirudin (1 mg/kg) ameliorates myocardial ischemia-reperfusion injury via inhibition of NLRP3-induced pyroptosis. Restores left ventricular function and reduces M1-macrophage polarization.
Por qué esto importa para la hirudoterapia
Este estudio investigó si la hirudina (1 mg/kg), descrita como un inhibidor eficaz de la trombina, mejora la lesión por isquemia-reperfusión miocárdica en un modelo de shock hemorrágico y resucitación (HSR) en rata. La hirudina restauró parcialmente la función ventricular izquierda, redujo los niveles séricos de CK-MB y cTnT, disminuyó los macrófagos polarizados a M1 y los factores asociados a piroptosis (caspasa-1 escindida, GSDMD N-terminal, IL-1β, IL-18), y el agonista de NLRP3 nigericina revirtió estos efectos cardioprotectores, lo que sugiere que el mecanismo involucra la inhibición de la piroptosis inducida por NLRP3. El resumen no describe la hirudina como derivada de sanguijuela, ni especifica la vía de administración. Se trata de un estudio en animales con dosis única y sin datos en humanos, y no se involucra ninguna aplicación de sanguijuelas; la conexión con la sanguijuela se basa únicamente en que la hirudina es un inhibidor de la trombina bien conocido.
Citación
Hirudin ameliorates myocardial ischemia-reperfusion injury in a rat model of hemorrhagic shock and resuscitation: roles of NLRP3-signaling pathway.
Bai Y et al. · Molecular and cellular biochemistry, 2023
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026