, Volume 41, Issue 3, pp 803–810 | Cite as

Ulinastatin Protects against CVB3-Induced Acute Viral Myocarditis through Nrf2 Activation

  • Fangqiang Song
  • Fanpo Kong
  • Hongqing Zhang
  • Yongqin Zhou
  • Ming Li


Inflammation and oxidative stress are implicated in the pathogenesis of acute viral myocarditis (AVM). Ulinastantin (UTI), an inhibitor of serine protease widely used in treatment of pancreatitis and various inflammatory disorders, displays cardioprotective properties in experimental animals. Although the specific mechanism through which UTI regulates cardiac function is not well explored, evidence suggests that UTI might activate nuclear factor E2-related factor 2 (Nrf2) signaling. In this study, we investigated the role of Nrf2 in mediating UTI’s cardioprotection in a mouse model of AVM. We found that UTI is an activator of Nrf2 signaling. It markedly increased Nrf2 nuclear translocation, Nrf2 transcription capacity, and the downstream protein expression. In addition, UTI possessed strong protective functions in coxsackievirus B3 (CVB3)-induced AVM. UTI treatment effectively reduced the cardiac damage, decreased the expression of inflammatory cytokines, and balanced oxidative stress via improving the activity of anti-oxidant and detoxifying enzymes. Even more impressively, UTI achieved its cardioprotective activities in an Nrf2-dependent manner. Taken together, our study has identified a novel pathway through which UTI exerts its cardioprotective functions and provides a molecular basis for UTI potential applications in the treatment of AVM and other inflammatory disorders.


ulinastatin myocarditis inflammation oxidative stress Nrf2 



acute viral myocarditis


nuclear factor E2-related factor-2




coxsackievirus B3


antioxidant response element


reactive oxygen species


heme oxygenase-1


NAD(P)H quinine oxidoreductase 1


left ventricular


end-systolic diameter


fractional shortening


LV diameter at end-diastole


LV diameter at end-systole


aspartate amino transferase


lactate dehydrogenase


creatine kinase




superoxide dismutase




glutathione peroxidase


tumor necrosis factor-α






Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Critical Care MedicineTengzhou Central People’s HospitalTengzhouChina
  2. 2.Department of UrologyTengzhou Central People’s HospitalTengzhouChina

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