2-(4-Methylthiazol-5-yl)ethyl nitrate hydrochloride(W1302)is a nitro containing derivative of clomethiazole,which is a novel neuroprotective agent with both carbon monoxide(NO)donor and weak y-aminobutyric acid type A(GABAA)receptor allosteric regulatory excitatory effect.The current study used a rat model of transient middle cerebral arteryocclusion(tMCAO)brain injury to evaluate the therapeutic effect of W1302 on ischemic stroke and explore its potential mechanisms of action.This experiment has been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica,Chinese Academy of Medical Sciences(ethical review forms No.620,632,5013).The results showed that gavage administration of 1,3,and 10 mg·kg-1 of W1302 can significantly reduce the volume of cerebral infarction in rats with ischemia for 2 h and reperfusion for 24 h,and the therapeutic effect was better than that of 200 mg·kg-1 of DL-3n-butylphthalide.W1302 significantly increased NO levels in blood and brain tissue.It increased cerebral blood flow and brain adenosine triphosphate(ATP)content after reperfusion,as well as,inhibited the expressions of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in brain tissue.The time window of W1302 was between 120-180 min after ischemia.These research results demonstrated that W1302 could increase NO release,dilate blood vessels,and increase cerebral blood flow,improve energy supply to brain tissue and increase ATP levels,and inhibit neuro-inflammation,which playing the protective roles in tMCAO stroke model rats.This provides theoretical support for the clinical application of W1302 in the treatment of ischemic stroke.
关键词
脑卒中/硝酸2-(4-甲基噻唑-5-基)乙酯盐酸盐/一氧化氮供体/GABAA受体激动剂/神经炎症
Key words
stroke/2-(4-methylthiazol-5-yl)ethyl nitrate hydrochloride/nitric oxide donor/γ-aminobutyric acid type A receptors agonist/neuro-inflammation
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