Ulinastatin is a potent multivalent
serine protease inhibitor, which was recently found with therapeutic potentials in treating
sepsis, and the most life-threatening complication of
critically ill population. However, the pharmacological features and possible mechanisms need to be further elucidated in reliable and clinical relevant
sepsis models. As known,
sepsis induced by surgery of cecal
ligation and
puncture (CLP) is widely accepted as the gold standard animal model, but the inconsistency of outcomes is the most obvious problem. In the present experiments, we reported an improved rat CLP model with much more consistent outcomes using self-made three edged
puncture needles in our lab. Results from this optimized model revealed that
ulinastatin improved survivals of CLP rats, attenuated proinflammatory response and prevented systemic disorder and organ dysfunction.
Ulinastatin was also found to be effective in ameliorating
sepsis-related ALI, a syndrome most frequent and fatal in
sepsis. The molecular mechanism investigation showed that
ulinastatin's protection against ALI was probably related to the down-regulation of NF-κB activity and inhibition of TNF-α,
IL-6 and
elastase expressions in the lung tissue. In conclusion, based on a successful establishment of optimized rat CLP model
ulinastatin is proved to be an effective candidate for
sepsis treatment, due to its anti-
inflammation and anti-
protease activities that ameliorate systemic disorders, prevent organ
injuries and thus improve the survival outcomes of
sepsis in animals.