Ulinastatin downregulates TLR4 and NF-kB expression and protects mouse brains against ischemia/reperfusion injury. (3rd April 2017)

• Record Type: Journal Article
• Authors: Li, Xiaofang; Su, Likai; Zhang, Xiangjian; Zhang, Cong; Wang, Lina; Li, Yaoru; Zhang, Ye; He, Tingting; Zhu, Xingyuan; Cui, Lili
• Is Part Of: Neurological research. Volume 39:Number 4(2017)
• Page Start: 367
• Page End: 373
• Publication Date: 2017-04-03
• Subjects: Cerebral ischemia/reperfusion -- ulinastatin -- inflammatory -- toll-like receptor 4 -- nuclear factor-kappa B; Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8005
• DOI: 10.1080/01616412.2017.1286541
• Languages: English
• ISSNs: 0161-6412

Abstract

Abstract: 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/100 g), and UTI-H (tMCAO + UTI 3000 U/100 g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. About 24 h 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-κB 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-κB. 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-κB expression.