Ulinastatin downregulates TLR4 and NF-kB expression and protects mouse brains against ischemia/reperfusion injury

Background: Inflammatory damage plays an important role in ischemic stroke and provides potential targets for therapy. Ulinastatin (UTI), a drug used to treat shock and acute pancreatitis in clinic, has attracted attention for its protective effects through immunomodulatory and anti-inflammatory properties. However, the effect of UTI in the acute phase of cerebral ischemia/reperfusion (I/R) is not clear. This study is to investigate the potential neuroprotective effect of UTI and explore its underlying mechanisms. Methods: Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly assigned into four groups: Sham (sham-operated) group, tMCAO (tMCAO+ 0.9% saline) group, UTI-L (tMCAO+UTI 1500 U/100g), and UTI-H (tMCAO+UTI 3000 U/100g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. About 24h after the reperfusion, the neurological deficit, brain water content, and infarct volume were detected. Immunohistochemistry, western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression of TLR4 and NF-B in the ischemic cerebral cortex. Results: Compared with tMCAO group, both UTI-L and UTI-H groups dramatically ameliorated neurological deficit (p<0.05), lessened the brain water content (p<0.05) and infarct volume (p<0.05), and decreased the expression of TLR4 and NF-B.Conclusion: These results showed that UTI protected the brain against ischemic injury which may be due to the alleviation of inflammation reaction in early stage through downregulating TLR4 and NF-B expression.