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Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

美满霉素改善血맜性痴呆大鼠认知功能损伤并抑制氧化应激

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Abstract

Objective

Nitric oxide (NO) was speculated to play an important role in the pathophysiology of cerebral ischemia. Minocycline, a tetracycline derivative, reduced inflammation and protected against cerebral ischemia. To study the neuroprotection mechanism of minocycline for vascular dementia, the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats.

Methods

The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO). Wistar rats were divideded into 3 groups randomly: sham-operation group (S group), vascular dementia model group (M group), and minocycline treatment group (MT group). The behaviour was tested with Morris water maze and open-field task. Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The optical density value was measured by imaging analysis. Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope.

Results

Minocycline attenuated cognitive impairment. Inducible NOS was significantly down-regulated in MT group, compared with that in M group (P < 0.01), while eNOS was significantly up-regulated, compared with that in M group (P < 0.01). The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P < 0.01).

Conclusion

Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia, which restrains apoptosis and oxidative stress to protect neural function.

摘要

目的

观察美满霉素(minocycline)对血맜性痴呆大鼠学习记忆功能和脑组织内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)、 诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)表达的影响, 探讨美满霉素对血맜性痴呆的脑保护作用的机制。

方法

Wistar大鼠随机分为假手术组(S 组)、 痴呆模型组(M 组)、 美满霉素治疗组(MT组)。 RT-PCR和免疫组织化学法检测大鼠脑组织eNOS、iNOS的表达, 行为学检测大鼠学习记忆功能的改变。

结果

M组与S组行为学检查显示, M组大鼠有显著学习记忆障碍(P < 0.01), MT组与M组比较行为学检测结果显示, MT 组大鼠学习记忆障碍有显著改善(P < 0.01)。 MT组iNOS表达较M组降低(P < 0.01), MT组eNOS表达较M组增高(P < 0.05); MT组eNOS、 iNOS表达较S组增高(P < 0.01); M组eNOS、 iNOS表达较S组显著增高(P < 0.01)。

结论

美满霉素能降低血맜性痴呆大鼠脑组织iNOS表达, 增强eNOS 表达, 抑制氧化应激反应, 发挥脑保护作用。

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Authors and Affiliations

  1. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, 400016, China

    Zhi-You Cai  (蔡志友), Yong Yan  (晏勇), Ning Yan  (晏宁), Fang Wu  (吴芳) & Jie-Ying Li  (李洁颖)

  2. Department of Anatomy, Chongqing Medical University, Chongqing, 400016, China

    Shan-Quan Sun  (孙善全)

  3. Department of Neurology, the Affiliated Hospital of Zunyi Medical College, Zunyi, 563003, China

    Jun Zhang  (张 骏) & Liang-Guo HUANG  (黄良国)

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  1. Zhi-You Cai  (蔡志友)
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Correspondence to Yong Yan  (晏勇).

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Cai, ZY., Yan, Y., Sun, SQ. et al. Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion. Neurosci. Bull. 24, 305–313 (2008). https://doi.org/10.1007/s12264-008-0324-y

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  • DOI: https://doi.org/10.1007/s12264-008-0324-y

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