安宫牛黄丸改善缺血性及出血性中风大鼠氧化应激的神经保护机制研究

doi:10.19803/j.1672-8629.20250745

摘要/Abstract

摘要： 目的探讨安宫牛黄丸改善缺血性及出血性中风模型大鼠氧化应激的神经保护机制。方法采用分子对接与分子动力学模拟技术,分析安宫牛黄丸中关键活性成分与脑源性神经营养因子（BDNF）及神经生长因子（NGF）的相互作用;分别建立脑缺血与脑出血大鼠模型,将动物随机分为假手术组、模型组、安宫牛黄丸低剂量组（257 mg·kg^-1）及高剂量组（514 mg·kg^-1）;通过生化法检测大鼠脑组织中丙二醛（MDA）含量和谷胱甘肽过氧化物酶（GSH-Px）活性;采用Western Blot法检测大鼠脑组织BDNF与NGF蛋白表达水平。结果分子对接结果显示,安宫牛黄丸中核心成分小檗碱与BDNF、黄芩苷与NGF均表现出良好结合活性,结合能均低于-5.0 kcal·mol^-1。分子动力学模拟进一步验证了小檗碱与BDNF、黄芩苷与NGF之间具有稳定的结合特征。动物实验表明,与模型组比较,安宫牛黄丸低剂量组大鼠脑组织中MDA水平显著降低（P<0.05）,GSH-Px含量显著升高（P<0.05）,BDNF和NGF蛋白表达亦显著上调（P<0.05）。结论安宫牛黄丸可能通过减轻氧化应激并上调BDNF/NGF通路,在缺血性及出血性中风模型中发挥神经保护作用。

关键词: 安宫牛黄丸, 缺血性中风, 出血性中风, 神经营养因子, 神经生长因子, 抗氧化, 分子对接, 大鼠

Abstract: Objective To investigate the neuroprotective mechanism through which Angong Niuhuang Wan mitigates oxidative stress in rats with ischemic and hemorrhagic stroke. Methods Molecular docking and molecular dynamics simulations were used to analyze the interactions between key active components of Angong Niuhuang Wan and the brain-derived neurotrophic factor (BDNF) and the nerve growth factor (NGF). Rat models of cerebral ischemia and cerebral hemorrhage were established before the animals were randomly divided into sham-operated, model, low-dose Angong Niuhuang Wan (257 mg·kg^-1), and high-dose Angong Niuhuang Wan (514 mg·kg^-1) groups. Malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels in brain tissues were measured using biochemical assays. Protein expression levels of BDNF and NGF were detected by Western blot. Results Molecular docking results showed that the core components of Angong Niuhuang Wan-berberine and baicalin-had good binding activity with BDNF and NGF, respectively, with binding energies below -5.0 kcal·mol^-1. Molecular dynamics simulations confirmed stable binding activity between berberine and BDNF, and between baicalin and NGF. Animal experiments suggested that in the low-dose Angong Niuhuang Wan groups, MDA levels were significantly reduced (P<0.05) GSH-Px contents increased (P<0.05) while protein expressions of BDNF and NGF were significantly up-regulated (P<0.05) in brain tissues of rats compared with the model group. Conclusion Angong Niuhuang Wan may exert neuroprotective effects in ischemic and hemorrhagic stroke models by reducing oxidative stress and upregulating the BDNF/NGF pathway.

Key words: Angong Niuhuang Wan, Ischemic Stroke, Hemorrhagic Stroke, Neurotrophic Factor, Nerve Growth Factor, Antioxidant, Molecular Docking, Rat

中图分类号:

李雪丽, 唐田, 白雪. 安宫牛黄丸改善缺血性及出血性中风大鼠氧化应激的神经保护机制研究[J]. 中国药物警戒, 2025, 22(12): 1345-1351.

LI Xueli, TANG Tian, BAI Xue. Neuroprotective Mechanisms of Angong Niuhuang Wan for Attenuating Oxidative Stress in Rat Models of Ischemic and Hemorrhagic Stroke[J]. Chinese Journal of Pharmacovigilance, 2025, 22(12): 1345-1351.

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