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

被引:99
作者
Li, Xiaofang [1 ]
Su, Likai [1 ]
Zhang, Xiangjian [2 ,3 ]
Zhang, Cong [2 ,3 ]
Wang, Lina [2 ,3 ]
Li, Yaoru [2 ,3 ]
Zhang, Ye [2 ,3 ]
He, Tingting [2 ,3 ]
Zhu, Xingyuan [2 ,3 ]
Cui, Lili [2 ,3 ]
机构
[1] Hebei Univ, Affiliated Hosp, Dept Neurol, Baoding, Peoples R China
[2] Hebei Med Univ, Hosp 2, Dept Neurol, Shijiazhuang, Peoples R China
[3] Hebei Med Univ, Hosp 2, Hebei Key Lab Neurol, Shijiazhuang, Peoples R China
基金
中国国家自然科学基金;
关键词
Cerebral ischemia/reperfusion; ulinastatin; inflammatory; toll-like receptor 4; nuclear factor-kappa B; TOLL-LIKE RECEPTORS; CEREBRAL-ARTERY OCCLUSION; KAPPA-B; MOLECULAR-MECHANISMS; INFLAMMATION; ISCHEMIA; STROKE; BLOOD; P-P38MAPK; CYTOKINES;
D O I
10.1080/01616412.2017.1286541
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:367 / 373
页数:7
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