摘 要
缺血性脑损伤是脑血管疾病中的常见类型，其发病率和死亡率在全球范围内均呈上升趋势。川芎嗪作为一种传统中药成分，具有显著的抗氧化和抗炎特性，近年来被广泛研究其在神经保护中的应用。本研究旨在探讨川芎嗪对缺血性脑损伤的保护效应及其潜在机制。通过建立大鼠中动脉闭塞（MCAO）模型，我们评估了川芎嗪在不同剂量下对脑梗死体积、神经功能评分以及氧化应激指标的影响。实验结果显示，川芎嗪治疗组的大鼠脑梗死体积显著减少，神经功能评分明显改善，同时氧化应激相关指标如丙二醛（MDA）水平降低，超氧化物歧化酶（SOD）活性增强。进一步的分子生物学研究表明，川芎嗪通过激活Nrf2/ARE信号通路，增强了内源性抗氧化系统的功能，从而减轻了缺血再灌注引起的氧化应激损伤。此外，川芎嗪还通过抑制NF-κB通路的激活，减少了炎症因子的释放，进一步保护了神经细胞免受炎症损害。本研究首次系统地揭示了川芎嗪在缺血性脑损伤中的多重保护机制，为临床应用提供了坚实的理论基础和实验依据。这些发现不仅扩展了我们对川芎嗪药理作用的理解，也为开发新型神经保护药物提供了新的方向。
关键词：缺血性脑损伤；川芎嗪；神经保护；氧化应激；炎症因子
Abstract
Ischemic brain injury is a common type of cerebrovascular disease, and its incidence and mortality are increasing around the world. As a traditional TCM ingredient, ligustrazine has remarkable antioxidant and anti-inflammatory properties and has been widely studied in neuroprotection. This study aimed to investigate the protective effects and underlying mechanisms of ligustrazine on ischemic brain injury. By developing the rat middle artery occlusion (MCAO) model, we evaluated the effect of ligustrazine on cerebral infarction volume, neurological function score, and oxidative stress index at different doses. The experimental results showed that the volume of cerebral infarction in the ligustrazine-treated rats was significantly reduced, the neurological function score was significantly improved, and the level of oxidative stress related indicators such as malondialdehyde (MDA) was reduced, and the activity of superoxide dismutase (SOD) was enhanced. Further molecular studies demonstrated that ligustrazine enhanced the function of the endogenous antioxidant system by activating the Nrf 2 / ARE signaling pathway, thereby alleviating the oxidative stress damage induced by ischemia and reperfusion. In addition, ligustrazine also reduced the release of inflammatory factors by inhibiting the activation of the NF- κ B pathway. This study is the first to systematically reveal the multiple protective mechanisms of ligustrazine in ischemic brain injury, providing a solid theoretical and experimental basis for clinical application. These findings not only extend our understanding of the pharmacological effects of ligustrazine, but also provide new directions for the development of novel neuroprotective drugs.
Keywords：Ischemic brain injury; Ligustrazine; Neuroprotection; Oxidative stress; Inflammatory factors
目 录
引 言 1
第一章 川芎嗪对缺血性脑损伤的分子机制 2
1.1 川芎嗪的化学成分分析 2
1.2 川芎嗪对神经细胞的保护作用 2
1.3 川芎嗪对炎症反应的影响 3
1.4 川芎嗪对氧化应激的调控作用 3
第二章 川芎嗪在动物模型中的保护效应 5
2.1 实验动物模型的建立与验证 5
2.2 川芎嗪给药方案的设计与实施 6
2.3 川芎嗪对脑组织病理学的影响 6
2.4 川芎嗪对神经功能恢复的作用评估 7
第三章 临床前研究中的安全性与有效性评估 8
3.1 川芎嗪的毒理学评价 8
3.2 川芎嗪的药代动力学研究 8
3.3 临床前研究的伦理考量 9
3.4 临床转化潜力分析 9
结 论 11
参考文献 12
致 谢 13
缺血性脑损伤是脑血管疾病中的常见类型，其发病率和死亡率在全球范围内均呈上升趋势。川芎嗪作为一种传统中药成分，具有显著的抗氧化和抗炎特性，近年来被广泛研究其在神经保护中的应用。本研究旨在探讨川芎嗪对缺血性脑损伤的保护效应及其潜在机制。通过建立大鼠中动脉闭塞（MCAO）模型，我们评估了川芎嗪在不同剂量下对脑梗死体积、神经功能评分以及氧化应激指标的影响。实验结果显示，川芎嗪治疗组的大鼠脑梗死体积显著减少，神经功能评分明显改善，同时氧化应激相关指标如丙二醛（MDA）水平降低，超氧化物歧化酶（SOD）活性增强。进一步的分子生物学研究表明，川芎嗪通过激活Nrf2/ARE信号通路，增强了内源性抗氧化系统的功能，从而减轻了缺血再灌注引起的氧化应激损伤。此外，川芎嗪还通过抑制NF-κB通路的激活，减少了炎症因子的释放，进一步保护了神经细胞免受炎症损害。本研究首次系统地揭示了川芎嗪在缺血性脑损伤中的多重保护机制，为临床应用提供了坚实的理论基础和实验依据。这些发现不仅扩展了我们对川芎嗪药理作用的理解，也为开发新型神经保护药物提供了新的方向。
关键词：缺血性脑损伤；川芎嗪；神经保护；氧化应激；炎症因子
Abstract
Ischemic brain injury is a common type of cerebrovascular disease, and its incidence and mortality are increasing around the world. As a traditional TCM ingredient, ligustrazine has remarkable antioxidant and anti-inflammatory properties and has been widely studied in neuroprotection. This study aimed to investigate the protective effects and underlying mechanisms of ligustrazine on ischemic brain injury. By developing the rat middle artery occlusion (MCAO) model, we evaluated the effect of ligustrazine on cerebral infarction volume, neurological function score, and oxidative stress index at different doses. The experimental results showed that the volume of cerebral infarction in the ligustrazine-treated rats was significantly reduced, the neurological function score was significantly improved, and the level of oxidative stress related indicators such as malondialdehyde (MDA) was reduced, and the activity of superoxide dismutase (SOD) was enhanced. Further molecular studies demonstrated that ligustrazine enhanced the function of the endogenous antioxidant system by activating the Nrf 2 / ARE signaling pathway, thereby alleviating the oxidative stress damage induced by ischemia and reperfusion. In addition, ligustrazine also reduced the release of inflammatory factors by inhibiting the activation of the NF- κ B pathway. This study is the first to systematically reveal the multiple protective mechanisms of ligustrazine in ischemic brain injury, providing a solid theoretical and experimental basis for clinical application. These findings not only extend our understanding of the pharmacological effects of ligustrazine, but also provide new directions for the development of novel neuroprotective drugs.
Keywords：Ischemic brain injury; Ligustrazine; Neuroprotection; Oxidative stress; Inflammatory factors
目 录
引 言 1
第一章 川芎嗪对缺血性脑损伤的分子机制 2
1.1 川芎嗪的化学成分分析 2
1.2 川芎嗪对神经细胞的保护作用 2
1.3 川芎嗪对炎症反应的影响 3
1.4 川芎嗪对氧化应激的调控作用 3
第二章 川芎嗪在动物模型中的保护效应 5
2.1 实验动物模型的建立与验证 5
2.2 川芎嗪给药方案的设计与实施 6
2.3 川芎嗪对脑组织病理学的影响 6
2.4 川芎嗪对神经功能恢复的作用评估 7
第三章 临床前研究中的安全性与有效性评估 8
3.1 川芎嗪的毒理学评价 8
3.2 川芎嗪的药代动力学研究 8
3.3 临床前研究的伦理考量 9
3.4 临床转化潜力分析 9
结 论 11
参考文献 12
致 谢 13
