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TLR4对大鼠急性脑梗死体积与Nrf2、HO-1表达水平的影响

The effect of TLR4 on cerebral infarction volume and expression levels of Nrf2 and HO-1 in acute cerebral infarction rats
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摘要 目的探讨Toll样受体4(TLR4)对大鼠急性脑梗死体积与核因子E2相关性因子2(Nrf2)、血红素加氧酶-1(HO-1)表达水平的影响。方法制备大鼠急性脑缺血模型后,比较模型组与TLR4特异性抑制剂-TAK-242组行为学及脑梗死体积、Nrf2、HO-1表达水平改变;通过Morris水迷宫实验比较不同组小鼠脑梗死后学习功能的恢复;TTC染色比较不同组脑梗死体积变化;免疫组织化学染色及Western Blot比较各组Nrf2、HO-1表达水平变化。结果与假手术组比较,模型组与TAK-242组潜伏期延长,穿越平台次数减少,同时TAK-242组潜伏期明显短于模型组(P<0.05);TAK-242组穿越平台的次数明显多于模型组(P<0.05)。TAK-242组脑梗死体积明显小于模型组(P<0.05)。Nrf2、HO-1主要表达在神经元与星形胶质细胞中。另外,假手术组Nrf2、HO-1的表达水平明显低于模型组与TAK-242组,同时TAK-242组Nrf2、HO-1的表达水平明显高于模型组。3组大鼠Nrf2、HO-1表达水平有明显差异(P<0.05),且TAK-242组Nrf2、HO-1的表达水平显著高于模型组(P<0.05)。结论通过TLR4特异性抑制剂-TAK-242干预可以显著改善大鼠急性脑缺血的神经功能,减小脑梗死体积,促进神经元与星形胶质细胞Nrf2、HO-1的表达。 Objective To investigate the effect of TLR4 on the volume and expression levels of Nrf2 and HO-1 in acute cerebral infarction rats.Methods The changes of behavior,infarct volume,Nrf2 and HO-1 expression levels between model group and TAK-242 group were compared after acute cerebral ischemia.The Morris water maze test was used to compare the recovery of learning function after injury among different groups,and the changes of infarct volume among different groups were compared with TTC staining,and the changes of Nrf2 and HO-1 expression levels among different groups were compared by immunohistochemistry and Western Blot.Results Compared with the sham group,the latency of the model group and the TAK-242 group was prolonged and the number of crossing platform decreased,while the latency of the TAK-242 group was significantly shorter than that of the model group(P<0.05),and the number of the TAK-242 group crossing the platform was significantly more than that of the model group(P<0.05).The volume of cerebral infarction in TAK-242 group was significantly smaller than that in model group(P<0.05).Nrf2 and HO-1 were mainly expressed in neuronal cells and astrocytes,and the expression levels of Nrf2 and HO-1 in the sham operation group were significantly lower than those in the model group and the TAK-242 group.At the same time,the expression levels of Nrf2 and HO-1 in the TAK-242 group were significantly higher than that in the model group.There was significant difference in the expression levels of Nrf2 and HO-1 among the three groups(P<0.05),and the expression levels of Nrf2 and HO-1 in group TAK-242 were significantly higher than those in the model group(P<0.05).Conclusion The intervention of TLR4 specific inhibitor-TAK-242 could significantly improve the neural function of acute cerebral ischemia injury in rats,reduce the infarct volume,and promote the expression levels of Nrf2 and HO-1 in neurons and astrocytes.
作者 贾复敏 魏衡 周瑞 余勇飞 徐子辉 尹虹祥 Jia Fumin;Wei Heng;Zhou Rui(Department of Neurology,Hubei Provincial Hospital of Integrated Chinese&Western Medicine,Wuhan 430015)
出处 《卒中与神经疾病》 2019年第1期13-16,共4页 Stroke and Nervous Diseases
作者简介 通讯作者:尹虹祥。
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