<br>丹红注射液通过增强神经发生、激活BDNF/AKT/CREB信号通路改善缺血性脑卒中大鼠神经功能,Biomedicine & Pharmacotherapy

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丹红注射液通过增强神经发生、激活BDNF/AKT/CREB信号通路改善缺血性脑卒中大鼠神经功能
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2023-05-17 , DOI: 10.1016/j.biopha.2023.114887
Lan Li ₁ , Jie-Hong Yang ₁ , Chang Li ₁ , Hui-Fen Zhou ₁ , Li Yu ₁ , Xiao-Long Wu ₁ , Yi-Hang Lu ₁ , Yu He ₁ , Hai-Tong Wan ₁

Affiliation

丹红注射液（DHI）是一种活血化瘀的中药注射剂，已广泛用于治疗中风。许多研究集中于 DHI 在急性缺血性脑卒中 (IS) 中的作用机制；然而，很少有研究彻底探讨其在恢复过程中的作用。在本研究中，我们旨在确定DHI对脑缺血后长期神经功能恢复的影响并探讨相关机制。采用大脑中动脉闭塞（MCAO）方法建立大鼠IS模型。使用神经严重程度评分、行为、脑梗塞体积和组织病理学评估 DHI 的疗效。进行免疫荧光染色以评估海马神经发生。构建了体外缺氧/复氧（OGD/R）细胞模型，并进行了蛋白质印迹分析以验证潜在机制。我们的结果表明，DHI 治疗大大减少了梗塞体积，促进了神经功能恢复并逆转了脑部病理变化。此外，DHI 通过增加神经干细胞的迁移和增殖以及增强突触可塑性来促进神经发生。此外，我们发现 DHI 的促神经源作用与脑源性神经营养因子 (BDNF) 表达的增加和 AKT/CREB 的激活有关，而这些作用可被 BDNF 抑制剂 ANA-12 和 LY294002 减弱。受体和 PI3K。这些结果表明 DHI 通过增强神经发生和激活 BDNF/AKT/CREB 信号通路来改善神经功能。

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Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway

Danhong injection (DHI) is a traditional Chinese medicine injection that promotes blood circulation and removes blood stasis and has been widely used in the treatment of stroke. Many studies have focused on the mechanism of DHI in acute ischemic stroke (IS); however, few studies have thoroughly explored its role during recovery. In this study, we aimed to determine the effect of DHI on long-term neurological function recovery after cerebral ischemia and explored the related mechanisms. Middle cerebral artery occlusion (MCAO) was used to establish an IS model in rats. The efficacy of DHI was assessed using neurological severity scores, behaviors, cerebral infarction volume and histopathology. Immunofluorescence staining was performed to assess hippocampal neurogenesis. An in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was constructed and western-blot analyses were performed to verify the underlying mechanisms. Our results showed that DHI treatment greatly reduced the infarct volume, promoted neurological recovery and reversed brain pathological changes. Furthermore, DHI promoted neurogenesis by increasing the migration and proliferation of neural stem cells, and enhancing synaptic plasticity. Moreover, we found that the pro-neurogenic effects of DHI were related to an increase in brain-derived neurotrophic factor (BDNF) expression and the activation of AKT/CREB, which were attenuated by ANA-12 and LY294002, the inhibitors of the BDNF receptor and PI3K. These results suggest that DHI improves neurological function by enhancing neurogenesis and activating the BDNF/AKT/CREB signaling pathways.

更新日期：2023-05-17

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