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雌二醇对鱼藤酮和 6-羟基多巴胺诱导的帕金森病的神经保护作用的机制评价。

Mechanistic evaluation of neuroprotective effect of estradiol on rotenone and 6-OHDA induced Parkinson's disease.

机构信息

Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

Department of Gerontology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

出版信息

Pharmacol Rep. 2017 Dec;69(6):1178-1185. doi: 10.1016/j.pharep.2017.06.008. Epub 2017 Jul 8.

DOI:10.1016/j.pharep.2017.06.008
PMID:29128798
Abstract

BACKGROUND

The present study was intended to investigate the protective effect of estradiol against Parkinson's disease through the use of rotenone-induced neurotoxicity model.

METHODS

To define the effect on the behavioral function, Tail suspension test, morris water maize test and cylinder tests were performed. Several biochemical and histological markers related to Parkinson's disease was determined in animal and cell culture models. To evaluate the effect of estradiol on the cellular architecture in rotenone-induced brain tissue, the histopathological examination was carried out by using Haemotoxylin and Eosin staining. Moreover, estradiol effect was also been investigated for its protective effect against Parkinson's disease using cell culture model with use of brain endothelial cells. The flowcytometric analysis was carried out to measure apoptosis in cell culture model.

RESULTS

The abnormal level of antioxidant enzymes and lipid peroxidation were regulated toward the normal intensity under the influence of estradiol. Furthermore, intracellular ROS level and apoptosis were found to be reduced following estradiol treatment. During the 6-OHDA induced PD, the level of antioxidant marker such as GSH, ROS and TRAP, found to be significantly modulated by the estradiol.

CONCLUSION

In view of the above results, it may be suggested that the estradiol may be as a useful therapeutic agent against rotenone-induced neurotoxicity such as Parkinson's disease.

摘要

背景

本研究旨在通过使用鱼藤酮诱导的神经毒性模型来研究雌二醇对帕金森病的保护作用。

方法

为了确定对行为功能的影响,进行了悬尾试验、水迷宫试验和圆筒试验。在动物和细胞培养模型中测定了几种与帕金森病相关的生化和组织学标志物。为了评估雌二醇对鱼藤酮诱导的脑组织细胞结构的影响,通过苏木精和伊红染色进行了组织病理学检查。此外,还使用脑内皮细胞的细胞培养模型研究了雌二醇对帕金森病的保护作用。通过流式细胞术分析测量细胞培养模型中的细胞凋亡。

结果

在雌二醇的影响下,抗氧化酶和脂质过氧化的异常水平被调节到正常强度。此外,发现雌二醇处理后细胞内 ROS 水平和细胞凋亡减少。在 6-OHDA 诱导的 PD 中,雌二醇显著调节了抗氧化标志物如 GSH、ROS 和 TRAP 的水平。

结论

鉴于上述结果,雌二醇可能是一种对抗鱼藤酮诱导的神经毒性(如帕金森病)的有用治疗剂。

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