四物汤对血管性痴呆大鼠的神经保护作用及其机制研究 |
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引用本文: | 韩 岚,季兆洁,陈卫东,许 钒,尹登科,李珊珊,彭代银. 四物汤对血管性痴呆大鼠的神经保护作用及其机制研究[J]. 安徽中医学院学报, 2015, 34(4): 69-73 |
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作者姓名: | 韩 岚 季兆洁 陈卫东 许 钒 尹登科 李珊珊 彭代银 |
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作者单位: | 安徽中医药大学药学院 安徽省现代中药重点实验室,安徽 合肥 230012 |
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基金项目: | 国家自然科学基金项目(81473387);安徽省自然科学基金项目(1408085QH163);安徽省高等学校自然科学优秀青年基金课题(Z2101201) |
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摘 要: | 目的 探讨四物汤对血管性痴呆(vascular dementia,VD)大鼠的保护作用及其机制。方法 将SD大鼠随机分为假手术组,模型组,四物汤高剂量(6 g/kg)、低剂量(3 g/kg)组,尼莫地平组(20 mg/kg),每组12只。采用大脑中动脉阻塞再灌注法复制大鼠VD模型,术后连续给予相应药物14 d。采用水迷宫实验观察VD大鼠学习能力和记忆能力;酶联免疫吸附法测定海马组织中乙酰胆碱酯酶(acetylcholinesterase,AChE)、5- 羟色胺(5- hydroxy tryptamine,5- HT)、内皮素- 1(endothelin- 1,ET- 1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的含量。腹主动脉取血检测血液流变学指标。苏木精- 伊红染色观察海马CA1区神经细胞形态学变化。结果 与模型组比较,四物汤高剂量组大鼠逃避潜伏期明显缩短(P<0.05),在目标象限距离百分比显著增加(P<0.05),海马AChE、ET- 1含量显著降低(P<0.05),5- HT、VEGF含量显著升高(P<0.05),全血黏度、血浆黏度和红细胞聚集指数显著降低(P<0.05)。四物汤高、低剂量组比较,仅血浆黏度和红细胞聚集指数的差异具有统计学意义(P<0.05)。与模型组比较,四物汤组海马CA1区锥体细胞缺失减轻,神经纤维排列整齐,仅少数细胞核固缩。结论 四物汤对VD具有一定的改善作用,其机制与改善神经递质,调节海马ET- 1、VEGF含量,改善血流状态有关。
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关 键 词: | 四物汤;血管性痴呆;乙酰胆碱酯酶;5- 羟色胺;内皮素- 1;血管内皮生长因子 |
Neuroprotective Effect and Action Mechanism of Siwu Decoction in Rats with Vascular Dementia |
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Affiliation: | School of Pharmacy, Anhui University of Chinese Medicine & Anhui Key Laboratory of Modern Chinese Materia Medica, Anhui Hefei 230012, China |
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Abstract: | Objective To investigate the neuroprotective effect and action mechanism of Siwu Decoction in rats with vascular dementia (VD). Methods Adult male Sprague- Dawley rats were randomly divided into sham- operation group, model group, high- and low- dose Siwu Decoction groups (40 and 20 g/kg), and nimodipine group (20 mg/kg), with 12 rats in each group. A rat model of VD was established through middle cerebral artery occlusion/reperfusion. After operation, these groups received respective treatments for 14 d. Their spatial learning and memory abilities were assessed using the Morris water maze. The levels of acetylcholinesterase (AChE), 5- hydroxytryptamine (5- HT), endothelin- 1 (ET- 1), and vascular endothelial growth factor (VEGF) in the hippocampal tissue were measured by enzyme- linked immunosorbent assay. Blood samples were collected from the abdominal aorta to measure hemorheological indices. The morphological changes of hippocampal CA1 neurons were observed by HE staining. Results Compared with the model group, the high- dose Siwu Decoction had significantly reduced escape latency (P<0.05), a significantly increased target quadrant ratio (P<0.05), significantly reduced hippocampal AChE and ET- 1 levels (P<0.05), significantly increased hippocampal 5- HT and VEGF levels, and significantly reduced whole blood viscosity, plasma viscosity, and erythrocyte aggregation index (P<0.05). There were significant differences only in plasma viscosity and erythrocyte aggregation index between the high- and low- dose Siwu Decoction groups (P<0.05). Compared with the model group, the Siwu Decoction groups had reduced loss of hippocampal CA1 pyramidal cells, ordered arrangement of nerve fibers, and karyopyknosis in few cells. Conclusion Siwu Decoction shows certain efficacy in the treatment of VD, and its action mechanism involves regulating hippocampal AChE, 5- HT, ET- 1, and VEGF and improving hemorheology. |
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Keywords: | Siwu Decoction vascular dementia acetylcholinesterase 5- Hydroxytryptamine endothelin- 1 vascular endothelial growth factor |
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