Ligustilide alleviates brain damage and improves cognitive function in rats of chronic cerebral hypoperfusion
Ligustilide alleviates brain damage and improves cognitive function in rats of chronic cerebral hypoperfusion
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藁本内酯减轻慢性脑灌注不足大鼠脑损伤并改善认知功能
DOI：
10.1016/j.jep.2012.09.014
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发表时间：
2012-11-21
影响因子：
5.4
通讯作者：
Zhu, Li
中科院分区：
文献类型：
--
作者：
Feng, Zhanbo;Lu, Yapeng;Zhu, Li
民族药理学意义：当归是治疗月经紊乱的常用中药，其主要脂类成分当归内酯(LIG)对永久性局灶性脑缺血和短暂性前脑缺血有一定的神经保护作用。目的：在前人工作的基础上，探讨LIG对慢性脑低灌流模型大鼠顶叶皮质和海马区的保护作用。材料与方法：采用永久性双侧颈总动脉结扎(2VO)造成慢性脑低灌流模型。术后第8天开始给予LIG(80 mg/kg)灌胃，连续7d。用Morris水迷宫评估它们的空间协作能力和记忆能力。迷宫实验6d后处死大鼠。用甲酚紫染色或用Neun(神经元核)、MAP-2(微管相关蛋白-2)、Caspase-3(半胱氨酸天冬氨酸氨基转移酶)和GFAP(GHAT纤维酸性蛋白)抗体进行标记。结果：LIG治疗7d后，2VO大鼠迷宫实验第3天开始逃避潜伏期缩短，游泳距离缩短，在靶象限的时间百分比增加。LIG可预防2VO大鼠顶叶皮质和海马区神经元丢失、树突损伤和神经元凋亡，并抑制低灌流刺激的星形胶质细胞激活和增殖。结论：LIG对慢性脑低灌注损伤具有明显的神经保护作用，其机制可能与其抗2VO大鼠大脑皮质和海马区神经元的凋亡和星形胶质细胞的增殖有关。提示LIG可作为预防血管性痴呆(VD)的有效药物。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
Ethnopharmacological relevance: Ligustilide (LIG), a main lipophilic component of Danggui (Chinese Angelica root, Radix Angelica sinensis) which is a popular used herb to treat menstrual disorders in traditional chinese medicine, has been reported to possess some neuroprotective effects on permanent focal ischemia and transient forebrain ischemia.Aim of the study: Based on previous work, we intended to investigate the protective effects of LIG on parietal cortex and hippocampus of rats in chronic cerebral hypoperfusion model.Materials and methods: Chronic cerebral hypoperfusion was induced by permanent, bilateral common carotid artery's occlusion (2VO). The rats were treated with LIG (80 mg/kg, by oral) from the eighth day after surgery for seven consecutive days. Their spatial teaming and memory abilities were assessed using the Morris water maze. After six days for maze test, rats were sacrificed. Coronal sections in cortex and hippocampus were stained with cresyl violet or labeled with NeuN (Neuronal Nuclei), MAP-2 (Microtubule-Associated Protein-2), Caspase-3 and GFAP (Ghat Fibrillary Acidic Protein) antibodies.Results: LIG treatment for seven days decreased escape latency and swimming distance of 2VO rats from the third day in maze tests, and increased percent time in the target quadrant. LIG prevented neuronal loss, dendrites damage and neuronal apoptosis in both parietal cortex and hippocampus of 2VO rats; and it also inhibited astrocytic activation and proliferation stimulated by hypoperfusion.Conclusions: These results demonstrate that LIG show obvious neuroprotective potential for treating chronic cerebral hypoperfusion injury, which may be attributed to its anti-apoptosis of neuron and anti-proliferation of astrocyte both in cortex and in hippocampus of 2VO rats. We suggest that LIG can be developed as an effective drugs for the prevention of vascular dementia (VD). (C) 2012 Elsevier Ireland Ltd. All rights reserved.