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  2. Hirudin ameliorates myocardial ischemia-reperfusion injury in a rat model of hemorrhagic shock and resuscitation: roles of NLRP3-signaling pathway

Hirudin ameliorates myocardial ischemia-reperfusion injury in a rat model of hemorrhagic shock and resuscitation: roles of NLRP3-signaling pathway

  • Mol Cell Biochem. 2023 Mar 29. doi: 10.1007/s11010-023-04717-z.
Yang Bai 1 Jing Bai 2 Peng Lu 3 Yu-Mo Jing 1 Wei-Chao Zheng 1 Lu-Ying Wang 4 Jian-Hua Wang 1 Feng Wang 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China.
  • 2 Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China.
  • 3 Department of Cardiovascular Disease, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Hebei University of Chinese Medicine, Cangzhou, China.
  • 4 Department of Anesthesia and Trauma Research, Department of Anesthesiology, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China.
  • 5 Department of Cardiovascular Disease, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China. ecoco2021@163.com.
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.

Keywords

Hemorrhage shock and resuscitation; Hirudin; Ischemia; NLRP3; Pyroptosis.

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