Oxymatrine downregulates TLR4, TLR2, MyD88, and NF-kappaB and protects rat brains against focal ischemia.
Oxymatrine downregulates TLR4, TLR2, MyD88, and NF-kappaB and protects rat brains against focal ischemia.
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DOI：
10.1155/2009/704706
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发表时间：
2009
影响因子：
4.6
通讯作者：
Yin J
中科院分区：
文献类型：
--
作者：
Fan H;Li L;Zhang X;Liu Y;Yang C;Yang Y;Yin J
炎症损伤在脑缺血发病机制中起重要作用，并可能成为治疗的靶点。Toll样受体4（TLR 4）、Toll样受体2（TLR 2）、髓样分化因子88（MyD 88）和核因子κ-B（NF-κB）与炎症反应有关。本课题组前期研究证实氧化苦参碱（oxymatrine，OMT）对缺血性脑损伤具有保护作用，其机制可能与抑制NF-κB表达有关。然而，关于OMT在缺血性卒中急性期的机制知之甚少。因此，我们研究了OMT的潜在的神经保护作用和潜在的机制。雄性Sprague-Dawley大鼠随机分为假手术组、生理盐水组和OMT治疗组。我们使用大脑中动脉闭塞（MCAO）模型，并在脑缺血后立即腹腔注射OMT，并在随后的日子每天一次。在MCAO后的时间点，测量脑含水量和梗死面积。采用免疫组化和RT-PCR方法检测缺血脑组织TLR 4、TLR 2、MyD 88和NF-κB B在基因和蛋白水平的表达。结果表明，OMT可能通过下调TLR 4、TLR 2、MyD 88和NF-κB的表达，对MCAO所致的脑损伤具有保护作用。
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-κB) 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-κB 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-κB 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-κB.
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