Inhibition of Notch signaling pathways contribute to neuroprotection effect by the combination of astragalus membranaceus and ligustrazine in rat model after thrombolysis of cerebral ischaemia

摘要

To investigate the neuroprotection effect of the combination of astragalus membranaceus and ligustrazine on thrombolysis after ischemic stroke and explore its mechanism basing on the Notch signaling pathway. Materials and methods: Focal cerebral ischemia models were induced by autologous thrombus of middle cerebral artery occlusion (MCAO). Male Sprague-Dawley (SD) rats were randomly divided into 3 experimental groups: MCAO group, Thrombolysis by rt-PA group, Thrombolysis+combination treatment group. Rt-PA (5mg/kg) was administrated 3h after MCAO onset and combination treatment of astragalus membranaceus and ligustrazine (0.1-0.2ml/100g) was administrated immediately after thrombolysis. Rats were sacrificed 3h and 24h after thrombolysis. The expression levels of Notch1, HES1 were detected by Western blotting (WB) and quantitative real-time PCR (RT-PCR). Results: Compared with those results of MCAO group and Thrombolysis by rt-PA group, Thrombolysis+ combination treatment group markedly decreased the expression of Notch1, HES1, in protein and mRNA, 3h after thrombolysis (P<0.01, P<0.01). And the trend of decrease was more pronounced at 24h (P<0.01, P<0.01). Conclusions: The findings demonstrate that the combination of astragalus membranaceus and ligustrazine might promote neuroprotection effect through down-regulation the activation of Notch1/HES1 signaling pathways.