Ulinastatin attenuates lipopolysaccharide-induced cardiac dysfunction by inhibiting inflammation and regulating autophagy

Ulinastatin exerts protective effects against lipopolysaccharide (LPS)-induced cardiac dysfunction. Autophagy has been demonstrated to serve an important role in sepsis-induced cardiomyopathy; however, whether ulinastatin has an anti-autophagic effect in sepsis requires further investigation. The present study aimed to determine the protective effects of ulinastatin on cardiac dysfunction and its role in autophagy during sepsis. C57BL/6J mice were randomly divided into a control, LPS and LPS + ulinastatin group, the survival status of the mice was observed every 6 h and the survival rate at each time point was calculated for 7 days. Furthermore, JC-1 dye and ELISAs were used to analyze the mitochondrial membrane potential (MMP) and serum cardiac troponin I (cTnI) levels, respectively. Western blotting and ELISAs were used to measure the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. In addition, the cardiac ultrastructure and the number of autophagosomes formed were visualized using transmission electron microscopy, and the pathological changes in the myocardial tissues were analyzed using hematoxylin & eosin staining. Finally, the expression levels of autophagy-related proteins were analyzed using western blotting and immunofluorescence staining. The current study indicated that ulinastatin significantly improved the survival rate of septic mice. It was suggested that ulinastatin may protect against LPS-induced myocardium injury through its anti-inflammatory activity, as decreased cTnI levels, increased MMP and decreased expression levels of TNF-α and IL-6 were all observed following ulinastatin treatment. Furthermore, the number of autophagosomes formed, and the expression levels of microtubule-associated protein light chain 3 and Beclin 1 were significantly decreased following ulinastatin treatment. It was further observed that ulinastatin suppressed LPS-induced autophagosome formation, as indicated by the accumulation of sequestosome 1/p62, and the elimination of lysosome-associated membrane glycoprotein 1. In conclusion, the results of the present study suggested that ulinastatin treatment may improve survival and exert a protective effect over LPS-induced cardiac dysfunction. Furthermore, this protective effect may be associated with its anti-inflammatory and anti-autophagic activity.