Oxymatrine downregulates TLR4, TLR2, MyD88, and NF-kappaB and protects rat brains against focal ischemia.
Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Toll-like receptor-4 (TLR4), toll-like receptor-2 (TLR2), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-B (NF-kappaB) have been linked to inflammatory reactions. Our previous studies have proved that oxymatrine (OMT) protected ischemic brain injury and this effect may be through the decreasing of NF-kappaB expression. However, little is known regarding the mechanism of OMT in the acute phase of ischemic stroke. We therefore investigated the OMT's potential neuroprotective role and the underlying mechanisms. Male, Sprague-Dawley rats were randomly divided into sham, saline and OMT treatment groups. We used a middle cerebral artery occlusion (MCAO) model and administered OMT intraperitoneally immediately after cerebral ischemia and once daily on the following days. At time points after MCAO, brain water content and infarct size were measured. Immunohistochemistry and RT-PCR were used to analyse the expression of TLR4, TLR2, MyD88, and NF-kappaB at gene and protein level in ischemic brain tissue. The result indicated that OMT protected the brain from damage caused by MCAO; this effect may be through downregulation of the TLR4, TLR2, MyD88, and NF-kappaB.
Fan
Hongguang
H
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
Li
Litao
L
Zhang
Xiangjian
X
Liu
Ying
Y
Yang
Chenhui
C
Yang
Yi
Y
Yin
Jing
J
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D015394:Molecular Structure; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D000093842:Matrines
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D018696:Neuroprotective Agents; D011807:Quinolizines; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C037573:oxymatrine; D000093842:Matrines