归芪聪志汤及其拆方对VD模型大鼠海马神经元HIF-1,VEGF和HO-1表达的影响

马春林; 陈杰; 崔淑梅; 朱凯敏; 李海龙; 吴红彦

doi:10.13422/j.cnki.syfjx.20181532

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归芪聪志汤及其拆方对VD模型大鼠海马神经元HIF-1,VEGF和HO-1表达的影响

药理 | 更新时间：2024-01-04

- 归芪聪志汤及其拆方对VD模型大鼠海马神经元HIF-1,VEGF和HO-1表达的影响
- Effect of Guiqi Congzhi Decoction and Its Disassembled Prescriptions on Expressions of HIF-1, VEGF and HO-1 in Hippocampus Area of Vascular Dementia Rats
- 中国实验方剂学杂志 2018年24卷第15期页码：143-148
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金地区基金项目（81660760）;兰州市2015年人才创新创业扶持项目（2015-RC-24）
- DOI：10.13422/j.cnki.syfjx.20181532
  中图分类号： R-332;R285.5
- 纸质出版日期：2018
- 稿件说明：
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马春林, 陈杰, 崔淑梅, 等. 归芪聪志汤及其拆方对VD模型大鼠海马神经元HIF-1,VEGF和HO-1表达的影响[J]. 中国实验方剂学杂志, 2018,24(15):143-148.

MA Chun-lin, CHEN Jie, CUI Shu-mei, et al. Effect of Guiqi Congzhi Decoction and Its Disassembled Prescriptions on Expressions of HIF-1, VEGF and HO-1 in Hippocampus Area of Vascular Dementia Rats[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(15): 143-148.
马春林, 陈杰, 崔淑梅, 等. 归芪聪志汤及其拆方对VD模型大鼠海马神经元HIF-1,VEGF和HO-1表达的影响[J]. 中国实验方剂学杂志, 2018,24(15):143-148. DOI： 10.13422/j.cnki.syfjx.20181532.

MA Chun-lin, CHEN Jie, CUI Shu-mei, et al. Effect of Guiqi Congzhi Decoction and Its Disassembled Prescriptions on Expressions of HIF-1, VEGF and HO-1 in Hippocampus Area of Vascular Dementia Rats[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(15): 143-148. DOI： 10.13422/j.cnki.syfjx.20181532.

摘要

目的：研究归芪聪志汤及其拆方对血管性痴呆（vascular dementia，VD）大鼠海马组织缺氧诱导因子-1α（HIF-1α），血管内皮生长因子（VEGF），及血红素加氧酶-1（HO-1）表达的影响，并探讨相关的作用机制。方法：Wistar大鼠称体质量后，按随机原则选出10只作为假手术组，将其余90只大鼠采用改良后的双侧颈动脉永久性结扎法制备VD大鼠模型，造模后，筛选成功模型大鼠54只随机分为6组，分别为模型组，阳性药组（吡拉西坦，3.6 g·kg-1），归芪聪志汤组（9.9 g·kg-1），活血通络组（拆方1组，9.9 g·kg-1），化痰解毒组（拆方2组，9.9 g·kg-1），补气养血组（拆方2组，9.9 g·kg-1），每组9只。连续灌胃28 d后，Morris水迷宫予以行为学检测，苏木素-伊红（HE）染色观察海马神经元的形态改变，采用实时荧光定量聚合酶链式反应（Real-time PCR）法和蛋白免疫印迹法（Western blot）分别检测大鼠海马HIF-1α，VEGF及HO-1 mRNA和蛋白的表达。结果：治疗4周后，与假手术组比较，VD模型组大鼠的平均逃避潜伏期明显延长、跨原平台次数明显减少（P<0.05），大鼠海马的HIF-1α，VEGF，HO-1 mRNA及蛋白表达水平明显升高（P<0.05），HE染色显示VD模型大鼠海马神经细胞损伤严重；与模型组比较，归芪聪志汤组与吡拉西坦组大鼠的逃避潜伏期均显著缩短、跨原平台次数均显著增加（P<0.05），大鼠海马的HIF-1α，VEGF，HO-1 mRNA和蛋白表达水平均显著升高（P<0.05），HE染色显示归芪聪志汤与吡拉西坦组大鼠海马神经细胞损伤减轻。结论：归芪聪志汤组改善VD模型大鼠的学习记忆能力优于各拆方组，其作用机制可能与上调HIF-1α，VEGF及HO-1因子的表达，减轻氧化应激损伤，激发脑内的损伤修复有关。

Abstract

Objective: To observe the effect of Guiqi Congzhi decoction and its disassembled prescription on expressions of hypoxia inducible factor-1α (HIF-1α)

vascular endothelial growth factor (VEGF) and haem oxygenase-1 (HO-1) in the hippocampus area of vascular dementia rats. Method: A vascular dementia rat model was established through permanent ligation of bilateral carotid arteries. After being weighed

10 rats were selected as the sham operated group according to the random principle. The remaining 90 rats were used for modeling

54 eligible rats were randomly divided into 6 groups after successfully modeling:model group

positive drug control group

Guiqi Congzhi decoction group

Huoxue Tongluo group (the disassembled prescription group 1)

Huatan Jiedu group (the disassembled prescription group 2)

invigorating Qi and nourishing blood group (the disassembled prescription group 3)

with 9 rats in each group. Drugs were administered to the rats through gastric perfusion once a day for 4 weeks. Then the behaviors of all of the rats were detected by Morris water maze

the morphological changes in hippocampal neurons were detected by hematoxylineosin(HE) staining

the expressions of HIF-1α

VEGF and HO-1 mRNA and protein in hippocampus were detected by Real-time fluorescence quantitative PCR(Real-time PCR) and Western blot. Result: After 4 weeks of treatment

compared with sham-operation group

the average escape latency period prolonged significantly and the number of cross-platforms were distinctly decreased in model group rats (P<0.05)

and the expressions of HIF-1α

VEGF

HO-1 mRNA and protein in hippocampus of model rats were significantly increased (P<0.05)

suggesting that the damage of hippocampal nerve cells was serious in model group rats according to HE staining; compared with the model group

the escape latencies of the Guiqi Congzhi decoction group and the control group were significantly shortened

and the number of cross-platforms was significantly increased (P<0.05)

the expressions of HIF-1α

VEGF

HO-1 mRNA and protein in the hippocampus of Guiqi Congzhi decoction group and positive control group rats were significantly increased (P<0.05)

suggestting that the damage of hippocampal nerve cells was alleviated in Guiqi Congzhi decoction group and control group. Conclusion: The Guiqi Congzhi decoction group show better learning and memory abilities than those of the disassembled prescription groups

and its mechanism of action may be related to up-regulation of HIF-1α

VEGF

and HO-1 factors

alleviation of oxidative stress

and initiation of damage repair in the brain.

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