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Abstract：
BACKGROUND: The inflammatory response is a key factor in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI), and anti-inflammatory interventions may offer a promising therapeutic strategy. Forsythoside B (FB) is a phenylethanoid glycoside isolated from Forsythiae fructus, which has been reported to have anti-inflammatory effects. However, the mechanism of the neuroprotective effect of FB on CIRI remains unclear.
METHODS: Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R). FB was administered intraperitoneally for 3 days prior to MCAO/R. Cerebral infarct volume and neurological deficit score were used as indices to evaluate MCAO/R injury. The serum levels of inflammatory factors and antioxidant enzymes were measured. The activation of silent information regulator 2 homolog 1 (Sirt1) and the inhibition of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) pathway were assessed through western blot and immunohistochemistry analysis. Furthermore, the rats were treated with Sirt1 shRNA 3 days before MCAO/R by stereotactical injection into the ipsilateral hemispheric region to assess the impact of Sirt1 knockdown on the protection of FB during MCAO/R.
RESULTS: FB reduced cerebral infarct volume and neurological deficit score in MCAO/R rats. FB reduced pathological changes and cell apoptosis in the hippocampal CA1 region and cortex on the ischemic side of rats. FB inhibited the serum levels of inflammatory factors and increased the activities of antioxidant enzymes. Further study showed that FB inhibited the activation of the NLRP3 pathway and induced Sirt1 activation.
CONCLUSIONS: FB demonstrated neuroprotective and anti-inflammatory effects by inhibiting the NLRP3 pathway through Sirt1 activation in CIRI.
METHODS: Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R). FB was administered intraperitoneally for 3 days prior to MCAO/R. Cerebral infarct volume and neurological deficit score were used as indices to evaluate MCAO/R injury. The serum levels of inflammatory factors and antioxidant enzymes were measured. The activation of silent information regulator 2 homolog 1 (Sirt1) and the inhibition of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) pathway were assessed through western blot and immunohistochemistry analysis. Furthermore, the rats were treated with Sirt1 shRNA 3 days before MCAO/R by stereotactical injection into the ipsilateral hemispheric region to assess the impact of Sirt1 knockdown on the protection of FB during MCAO/R.
RESULTS: FB reduced cerebral infarct volume and neurological deficit score in MCAO/R rats. FB reduced pathological changes and cell apoptosis in the hippocampal CA1 region and cortex on the ischemic side of rats. FB inhibited the serum levels of inflammatory factors and increased the activities of antioxidant enzymes. Further study showed that FB inhibited the activation of the NLRP3 pathway and induced Sirt1 activation.
CONCLUSIONS: FB demonstrated neuroprotective and anti-inflammatory effects by inhibiting the NLRP3 pathway through Sirt1 activation in CIRI.
摘要：
背景：炎症反应是脑缺血/再灌注损伤（CIRI）发病的关键因素，和抗炎干预可能提供一个有希望的治疗策略。连翘苷B（FB）是从连翘中分离出的苯乙醇苷，据报道具有抗炎作用。然而,FB对CIRI的神经保护作用机制尚不清楚。
方法：成年雄性Sprague-Dawley大鼠进行短暂的大脑中动脉阻塞/再灌注（MCAO/R）。在MCAO/R之前，腹膜内施用FB3天。以脑梗死体积和神经功能缺损评分作为评价MCAO/R损伤的指标。检测血清炎症因子和抗氧化酶水平。通过蛋白质印迹和免疫组织化学分析评估了沉默信息调节因子2同源物1（Sirt1）的激活和具有pyrin结构域3（NLRP3）途径的核苷酸结合寡聚化结构域样受体的抑制。此外，在MCAO/R前3天，通过立体定向注射到同侧半球区域，用Sirt1shRNA治疗大鼠，以评估Sirt1敲低对MCAO/R期间FB保护的影响。
结果：FB降低了MCAO/R大鼠的脑梗死体积和神经功能缺损评分。FB减轻年夜鼠缺血侧海马CA1区和皮质的病理变化和细胞凋亡。FB抑制血清炎症因子水平,增加抗氧化酶活性。进一步研究表明，FB抑制NLRP3通路的激活并诱导Sirt1激活。
结论：FB通过在CIRI中激活Sirt1抑制NLRP3通路，显示出神经保护和抗炎作用。
方法：成年雄性Sprague-Dawley大鼠进行短暂的大脑中动脉阻塞/再灌注（MCAO/R）。在MCAO/R之前，腹膜内施用FB3天。以脑梗死体积和神经功能缺损评分作为评价MCAO/R损伤的指标。检测血清炎症因子和抗氧化酶水平。通过蛋白质印迹和免疫组织化学分析评估了沉默信息调节因子2同源物1（Sirt1）的激活和具有pyrin结构域3（NLRP3）途径的核苷酸结合寡聚化结构域样受体的抑制。此外，在MCAO/R前3天，通过立体定向注射到同侧半球区域，用Sirt1shRNA治疗大鼠，以评估Sirt1敲低对MCAO/R期间FB保护的影响。
结果：FB降低了MCAO/R大鼠的脑梗死体积和神经功能缺损评分。FB减轻年夜鼠缺血侧海马CA1区和皮质的病理变化和细胞凋亡。FB抑制血清炎症因子水平,增加抗氧化酶活性。进一步研究表明，FB抑制NLRP3通路的激活并诱导Sirt1激活。
结论：FB通过在CIRI中激活Sirt1抑制NLRP3通路，显示出神经保护和抗炎作用。
