当前位置: X-MOL 学术Neurochem. Int. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Neuroprotection of edaravone on the hippocampus of kainate-induced epilepsy rats through Nrf2/HO-1 pathway
Neurochemistry international ( IF 4.2 ) Pub Date : 2017-07-08 , DOI: 10.1016/j.neuint.2017.07.001
Zhiguang Liu , Chengzhi Yang , Xinyan Meng , Zaili Li , Cunling Lv , Peiwei Cao

Epilepsy is a severe and chronic neurological disease. Edaravone is an effective free radical scavenger and has been reported to prevent neuronal loss induced by Kainate (KA). However, the molecular mechanisms by which edaravone inhibits KA-induced neuron injury remain elusive. Seventy adult male Wistar rats were randomly divided into 7 groups. For KA treatment, Kainate (4 μg/kg) were administrated in the right hippocampus CA3 region with sereotactic technique. And for edaravone treatment, the rats were intraperitoneal injection with edaravone (10 mg kg - 1 d – 1). All rats were sacrificed on the seven day after the injection of KA. Histological changes of the hippocampus, CA1, CA3 and CA4 were observed under thionine staining. Histological changes of CA1 and CA3 were divided into the following 4 grades (histological grade,HG) under light microscope. The release of inflammatory cytokines was measured by ELISA assay. The inflammatory proteins and Nrf2 and HO-1 expression were determined by quantitative real time PCR (qRT-PCR) and Western blots analysis. Treatment with edaravone increased the neuronal density and decreased the neuronal damage degree in the CA1, CA3 subfield induced by KA. Besides, edaravone reduced the downregulation of the mRNA and protein expression levels of Nrf2 and HO-1 induced by KA. Moreover, edaravone decreased the levels of NF-κB (P65) and proinflammatory cytokines TNF-α, IL-1β and IL-6 and the inflammatory proteins expression levels, HMGB1, nNOS, iNOS and eNOS in the hippocampus. However, introduction of Nrf2-siRNA and HO-1 inhibitor (Znpp) reversed the effects of edaravone on KA-injected rats. Edaravone can protect hippocampal neurons from damage in KA-induced epilepsy rats through Nrf2/HO-1 pathway.



中文翻译:

依达拉奉通过Nrf2 / HO-1途径对海藻酸酯诱导的癫痫大鼠海马的神经保护

癫痫病是一种严重的慢性神经系统疾病。依达拉奉是一种有效的自由基清除剂,据报道可预防海因酸酯(KA)诱导的神经元丢失。但是,依达拉奉抑制KA诱导的神经元损伤的分子机制仍然难以捉摸。将70只成年雄性Wistar大鼠随机分为7组。对于KA治疗,通过立体定向技术在右海马CA3区施用海因酸盐(4μg/ kg)。对于伊达拉奉治疗,大鼠腹腔注射伊达拉奉(10 mg kg -1  d – 1)。注射KA后7天,将所有大鼠处死。在硫氨酸染色下观察海马,CA1,CA3和CA4的组织学变化。在光学显微镜下,CA1和CA3的组织学变化分为以下4个等级(组织学等级,HG)。通过ELISA测定法测量炎性细胞因子的释放。通过定量实时PCR(qRT-PCR)和蛋白质印迹分析确定炎性蛋白和Nrf2和HO-1表达。依达拉奉治疗可增加KA诱导的CA1,CA3子域的神经元密度,并降低其神经元损伤程度。此外,依达拉奉降低了KA诱导的Nrf2和HO-1的mRNA和蛋白表达水平的下调。此外,依达拉奉降低了NF-κB(P65)和促炎细胞因子TNF-α的水平,海马中的IL-1β和IL-6以及炎症蛋白表达水平HMGB1,nNOS,iNOS和eNOS。然而,Nrf2-siRNA和HO-1抑制剂(Znpp)的引入逆转了依达拉奉对注射KA的大鼠的影响。依达拉奉可通过Nrf2 / HO-1途径保护海马神经元免受KA诱发的癫痫大鼠的伤害。

更新日期:2017-07-08
down
wechat
bug