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小檗碱通过抑制实验性自身免疫性脑脊髓炎中基质金属蛋白酶-9和层粘连蛋白降解对神经元损伤的保护作用。

The protective effect of berberine against neuronal damage by inhibiting matrix metalloproteinase-9 and laminin degradation in experimental autoimmune encephalomyelitis.

作者信息

Jiang Ying, Wu Aiming, Zhu Cansheng, Pi Rongbiao, Chen Shaoqiong, Liu Yingying, Ma Lili, Zhu Dongliang, Chen Xiaohong

机构信息

Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

Neurol Res. 2013 May;35(4):360-8. doi: 10.1179/1743132812Y.0000000156.

Abstract

OBJECTIVE

This study aims to assess the protective effect of berberine against neuronal damage in the brain parenchyma of mice with experimental autoimmune encephalomyelitis (EAE).

METHODS

EAE was induced in female C57 BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide. The berberine treatment was initiated on the day of disease onset and administered daily until the mice were sacrificed. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, gelatin gel, and gelatin in situ zymography were analysed in this study.

RESULTS

Berberine reduced the TUNEL-positive neuronal cells of EAE mice. Gelatin gel and gelatin in situ zymography showed up-regulation of gelatinase activity, which was mainly located in neurons and colocalized with remarkable laminin degradation in EAE mice. Berberine significantly inhibited gelatinase activity and reduced the laminin degradation in EAE mice.

DISCUSSION

Our data suggest that berberine could provide protection against neuronal damage in EAE by inhibiting gelatinase activity and reducing laminin degradation. These findings provide further support that berberine can be a potential therapeutic agent for multiple sclerosis.

摘要

目的

本研究旨在评估小檗碱对实验性自身免疫性脑脊髓炎(EAE)小鼠脑实质神经元损伤的保护作用。

方法

用髓鞘少突胶质细胞糖蛋白35 - 55氨基酸肽诱导雌性C57 BL/6小鼠发生EAE。在疾病发作当天开始给予小檗碱治疗,每天给药,直至处死小鼠。本研究分析了末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记(TUNEL)检测、明胶凝胶和明胶原位酶谱分析。

结果

小檗碱减少了EAE小鼠TUNEL阳性神经元细胞。明胶凝胶和明胶原位酶谱分析显示EAE小鼠中明胶酶活性上调,其主要位于神经元中,并与显著的层粘连蛋白降解共定位。小檗碱显著抑制EAE小鼠的明胶酶活性并减少层粘连蛋白降解。

讨论

我们的数据表明,小檗碱可通过抑制明胶酶活性和减少层粘连蛋白降解来保护EAE中的神经元损伤。这些发现进一步支持小檗碱可能是治疗多发性硬化症的潜在药物。

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