鹿茸提取物对血管性痴呆大鼠模型的治疗作用及其机制
| 作者: |
1董晗,
1黄卫新,
2胡亚男,
1王越晖,
3赵建军
1 吉林大学第一医院老年病科，长春 130021 2 长春中医药大学基础医学院，长春 130117 3 长春中医药大学附属医院脑病中心，长春 130117 |
| 通讯: |
王越晖
Email: yuehuiwang300@hotmail.com |
| DOI: | 10.3978/j.issn.2095-6959.2019.10.005 |
| 基金: | 吉林省卫生厅课题 (2014Q030)。 |
摘要
目的：研究鹿茸提取物对血管性痴呆(vascular dementia，VaD) 大鼠模型的治疗作用及其机制。 方法：选取120只Wistar大鼠，通过结扎双侧颈总动脉造模，将大鼠随机分为假手术组、模型组、西药组(盐酸多奈哌齐：0.45 mg/kg )、中药不同剂量组(鹿茸提取物：5~20 mg/kg )。术后3 d开始灌胃，连续28 d。采用水迷宫实验分析大鼠定航及空间探索能力变化，HE染色评价海马区细胞形态学改变，免疫组织化学判断Bcl-2表达水平变化，蛋白质印迹法测定蛋白激酶R样内质网激酶(protein kinase R-like endoplasmic reticulum kinase，PERK)、真核细胞起始因子2α(eukar yotic initiation factor 2α，EIf2α)表达水平变化。结果：与模型组相比，鹿茸提取物可使VaD大鼠定向航行能力及空间探索能力得到显著改善。HE染色提示鹿茸提取物不同剂量组大鼠海马细胞形态和排列方面有不同程度改善。免疫组织化学结果显示鹿茸提取物处理后可提高大鼠海马细胞Bcl-2的表达。蛋白质印迹法显示鹿茸提取物可下调PERK，EIf2α的表达。结论：鹿茸提取物对大鼠VaD模型具有一定治疗作用，其机制可能与抑制PERK/EIf2α、上调Bcl-2表达有关。鹿茸提取物可能是治疗VaD的潜在药物。
关键词：
鹿茸提取物；血管性痴呆；治疗作用；分子机制
Therapeutic effect of pilose antler extract on vascular dementia rat model and its mechanisms
CorrespondingAuthor: WANG Yuehui Email: yuehuiwang300@hotmail.com
DOI: 10.3978/j.issn.2095-6959.2019.10.005
Foundation: This work was supported by the Program from Health Commission of Jilin Province (2014Q030), China.
Abstract
Objective: To study the therapeutic effect of pilose antler extract on vascular dementia (VaD) and its mechanisms in rat model. Methods: One-hundred and twenty Wistar rats were randomly divided into the sham operation group, the model group, the western medicine group (donepezil hydrochloride: 0.45 mg/kg) and the Chinese herb group (pilose antler extract: 5–20 mg/kg). VaD model was established by bilateral common carotid artery ligation. Treatment was administrated by gavage from the third day post operation for 28 consecutive days. Water maze test was used to analyze the changes of navigation and space exploration ability in rats. HE staining was utilized to evaluate the morphological changes of hippocampal cells. Immunohistochemistry was used to evaluate the expression of Bcl-2. Western blot was used to detect the expression of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2α (EIf2α). Results: Compared with the model group, pilose antler extract could significantly improve the directional navigation and space exploration ability of VaD rats. HE staining showed that the morphology and arrangement of hippocampal cells of rats in different dosage groups of pilose antler extract were improved in varying degrees. Immunohistochemistry showed that pilose antler extract could increase the expression of Bcl-2 in rat hippocampal cells. Western blot showed that the pilose antler extract could down-regulate the expression of PERK and EIf2α. Conclusion: Pilose antler extract has a certain therapeutic effect on VaD model in rats. Its mechanism may be related to the inhibition of PERK/EIf2α and the up-regulation of Bcl-2 expression. Therefore, pilose antler extract may be a potential drug for the treatment of VaD.
Keywords：
pilose antler extract; vascular dementia; therapeutic effects; molecular mechanisms