The effect of focal cerebral ischemia-reperfusion injury on TLR4 and NF-κB signaling pathway.

The effect of focal cerebral ischemia-reperfusion injury on TLR4 and NF-κB signaling pathway.
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局灶性脑缺血再灌注损伤对TLR4和NF-κB信号通路的影响。

DOI:
10.3892/etm.2017.5463
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发表时间:
2018-01
影响因子:
2.7
通讯作者:
Xu B
Xu B
中科院分区:
医学4区
文献类型:
--
作者:
Chen J;Yang C;Xu X;Yang Y;Xu B

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本研究分析了大鼠局灶性脑缺血再灌注损伤模型中Toll样受体4(Toll样受体4,TLR4)和核因子-κB(NF-κB,核转录因子B)表达的变化。随机选择SD大鼠36只,分为假手术组(S组)、对照组(C组)和菊花酯组(核因子-κB抑制剂,CE组),每组12只。建立大鼠局灶性脑缺血再灌注模型。采用双盲法记录大鼠的生理指标和神经严重度评分。脑片三苯基四氮唑(TTC)染色评价脑梗塞面积。TUNEL法检测细胞凋亡率。半定量聚合酶链式反应和免疫印迹分析检测TLR4和NF-κB的表达。C组和CE组大鼠神经功能严重程度评分明显低于S组(P&lt;0.01)。TTC染色结果显示,C组和CE组均有不同程度的脑梗塞,但CE组的梗塞面积明显小于C组(P&lt;0.01)。CE组TUNEL阳性细胞数明显低于C组(P<0.01)。半定量聚合酶链式反应和免疫印迹分析结果显示,S组大鼠肺组织中NF-κB和TLR4的表达明显低于C组和CE组(P<0.01),CE组的NF-κB和TLR4的相对表达明显低于C组(P<0.01)。CE组和C组的NF-κB p65/p50表达明显高于S组(P<0.01)。结论:大鼠局灶性脑缺血再灌注损伤可引起脑组织损伤和细胞凋亡。其作用机制可能与上调NF-κB和TLR4的表达,激活TLR4/NF-κB信号通路有关。
The present study analyzed the change of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) expression in focal cerebral ischemia-reperfusion injury model. A sample of 36 Sprague-Dawley rats were randomly selected and divided into sham operation group (group S), control group (group C) and Chrysanthemum ester group (NF-κB inhibitor, group CE), each group consisted of 12 rats. The rat model of focal cerebral ischemia-reperfusion was established. The physiological indexes and neurological severity score of rats was recorded by a double-blind method. The cerebral infarction area was evaluated by triphenyltetrazole oxide (TTC) staining on brain slices. Apoptosis was evaluated by TUNEL staining. Semi-quantitative PCR and western blot analysis was used to measure the expression of TLR4 and NF-κB. The neurological severity score of rats in group C and CE were found to be significantly lower than group S (P<0.01). The TTC staining results showed that group C and CE had different levels of cerebral infarction but the area of infarction in group CE was significantly lower than group C (P<0.01). In addition, the number of TUNEL positive cells in group CE was significantly lower than group C (P<0.01). Semi-quantitative PCR and westernblot analysis results showed that the expression of NF-κB and TLR4 of group S was significantly lower than that of group C and group CE (P<0.01), the relative expression of NF-κB and TLR4 of group CE was significantly lower than that of group C (P<0.01). Moreover, the expression of NF-κB p65/p50 of group CE and group C was significantly higher than that of group S (P<0.01). This study concludes that the focal cerebral ischemia-reperfusion injury in rats can cause brain damage and cell apoptosis. This effect might be associated to the increased expression of NF-κB and TLR4, and the activation of TLR4/NF-κB signaling pathway.
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影响因子: 2.2
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DOI: 10.1021/acs.jmedchem.5b00671
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