Erythropoietin ameliorates severe hemorrhagic shock-induced serum proinflammatory cytokines and biochemical changes in spontaneously hypertensive rats

摘要

Objective Hypertensive patients have higher mortality rates from hemorrhagic shock (HS) than normotensive patients. HS can produce several proinflammatory mediators such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), leading to multiple organ dysfunction and death. Erythropoietin (EPO) has pleiotropic cytoprotective actions. We investigated the effects of EPO (300 U/kg) treatment on HS-induced serum proinflammatory cytokines and biochemical changes in spontaneously hypertensive rats (SHRs). Materials and Methods Severe HS was induced by withdrawing 60% of the rat’s total blood volume via a femoral arterial catheter (6 mL/100 g body weight) over 30 minutes. The mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 2 hours after the start of blood withdrawal. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), creatine phosphokinase (CPK), lactate, TNF-α, and IL-6 were measured 1 hour after HS had been induced. Results HS significantly increased HR and blood GOT, GPT, BUN, Cre, CPK, lactate, TNF-α, and IL-6 levels, and decreased hemoglobin level and MAP, in SHRs. Pretreatment with EPO improved the survival rate at 2 hours, preserved the MAP, decreased tachycardia and markers of organ injury (GOT, GPT, BUN, Cre, CPK, lactate), and suppressed the release of TNF-α and IL-6 after HS in SHRs. Conclusion Pretreatment with EPO suppresses the release of serum TNF-α and IL-6, and decreases the levels of markers of organ injury associated with HS in SHRs.