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改良补阳还五汤(一种多草药配方药物)对全脑缺血大鼠模型海马神经元损伤的影响。

Effect of modified Bo-yang-Hwan-o-Tang, a polyherbal medicine on the hippocampal neuronal damage in a rat model of global ischemia.

作者信息

Oh Tae Woo, Jung Hyo Won, Park Yong-Ki

机构信息

Department of Herbology, College of Korean Medicine, Gyeongju 780-714, Republic of Korea.

Department of Herbology, College of Korean Medicine, Gyeongju 780-714, Republic of Korea ; Korean Medicine R&D Center, Dongguk University, Gyeongju 780-714, Republic of Korea.

出版信息

Pharmacogn Mag. 2015 Jul-Sep;11(43):665-73. doi: 10.4103/0973-1296.160445.

Abstract

BACKGROUND

Chronic cerebral hypoperfusion has been well-characterized as a common pathological status contributing to vascular dementia (VD). In this study, the neuroprotective effect of modified Bo-yang-Hwan-O Tang (mBHT), a polyherbal medicine for ischemic stroke, was investigated in a rat model for global ischemia.

MATERIALS AND METHODS

Global ischemia model was prepared in Sprague-Dawley rats by the permanent occlusion of bilateral common carotid arteries (two-vessel occlusion [2VO])-induced chronic cerebral hypoperfusion. mBHT at doses of 250 and 500 mg/kg was orally administrated for 4 weeks once a day, 24 h after 2VO. Histopathological change of the hippocampal region was observed by hematoxylin and eosin, Nissl, and Fluoro-Jade B staining and immunohistochemistry with anti-glial fibrillary acidic protein and anti-neuronal nuclei antibodies. The expression of Bax, Bcl-2, and caspase-3 was investigated in the hippocampus by Western blot. The nuclear factor-kappa B (NF-κB) expression was also analyzed in hippocampal CA1 region using immunofluorescence staining.

RESULTS

The administration of mBHT at doses of 250 and 500 mg/kg significantly inhibited chronic cerebral hypoperfusion-induced neuronal damage and astroglial activation in the hippocampal CA1 region in 2VO rats. mBHT increased the NF-κB expression in the CA1 neuronal cells but decreased in activated astrocytes. In addition, mBHT significantly decreased the hippocampal expression of Bax and caspase-3 and increased the Bcl-2 expression in 2VO rats.

CONCLUSIONS

Our data indicate that mBHT has a neuroprotective property in VD induced by chronic cerebral hypoperfusion through inhibiting the hippocampal neuronal damage and astrogliosis.

摘要

背景

慢性脑灌注不足已被充分表征为导致血管性痴呆(VD)的一种常见病理状态。在本研究中,在全脑缺血大鼠模型中研究了改良的补阳还五汤(mBHT)(一种用于缺血性中风的多草药药物)的神经保护作用。

材料与方法

通过永久性闭塞双侧颈总动脉(双血管闭塞[2VO])诱导慢性脑灌注不足,在Sprague-Dawley大鼠中制备全脑缺血模型。在2VO后24小时,每天一次口服给予剂量为250和500mg/kg的mBHT,持续4周。通过苏木精和伊红染色、尼氏染色、荧光金B染色以及使用抗胶质纤维酸性蛋白和抗神经元核抗体的免疫组织化学观察海马区的组织病理学变化。通过蛋白质免疫印迹法研究海马中Bax、Bcl-2和caspase-3的表达。还使用免疫荧光染色分析海马CA1区中的核因子-κB(NF-κB)表达。

结果

给予剂量为250和500mg/kg的mBHT可显著抑制2VO大鼠海马CA1区慢性脑灌注不足诱导的神经元损伤和星形胶质细胞活化。mBHT增加了CA1神经元细胞中的NF-κB表达,但在活化的星形胶质细胞中降低。此外,mBHT显著降低了2VO大鼠海马中Bax和caspase-3的表达,并增加了Bcl-2的表达。

结论

我们的数据表明,mBHT通过抑制海马神经元损伤和星形胶质细胞增生,对慢性脑灌注不足诱导的VD具有神经保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e28/4522858/563526eeae39/PM-11-665-g001.jpg

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