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

Autor: Ye Zhang, Xingyuan Zhu, Cong Zhang, Lina Wang, Xiangjian Zhang, Likai Su, Lili Cui, Yaoru Li, Xiaofang Li, Tingting He
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
medicine.medical_treatment
Drug Evaluation
Preclinical
Ischemia
Down-Regulation
Brain Edema
Pharmacology
urologic and male genital diseases
Neuroprotection
Mice
Random Allocation
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Animals
RNA
Messenger
Saline
Glycoproteins
business.industry
NF-kappa B
Brain
Infarction
Middle Cerebral Artery
General Medicine
bacterial infections and mycoses
medicine.disease
Ulinastatin
female genital diseases and pregnancy complications
Toll-Like Receptor 4
Disease Models
Animal
Neuroprotective Agents
030104 developmental biology
Neurology
chemistry
Reperfusion Injury
Anesthesia
Shock (circulatory)
TLR4
Acute pancreatitis
Neurology (clinical)
medicine.symptom
business
Reperfusion injury
030217 neurology & neurosurgery
Zdroj: Neurological Research. 39:367-373
ISSN: 1743-1328
0161-6412
DOI: 10.1080/01616412.2017.1286541
Popis: 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.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.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.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.
Databáze: OpenAIRE
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