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Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model

美满霉素抑制血管性认知功能损伤大鼠海马星型胶质细胞激活和神经炎症

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Abstract

Objective

To study the neuroprotective mechanism of minocycline against vascular cognitive impairment after cerebral ischemia.

Methods

The rat model with vascular cognitive impairment was established by permanent bilateral common carotid artery occlusion (BCCAO). The observing time-points were determined at 4, 8 and 16 weeks after BCCAO. Animals were randomly divided into sham-operated group (n = 6), model group (subdivided into 3 groups: 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6), and minocycline group (subdivided into 3 groups: 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6). Minocycline was administered by douche via stomach after BCCAO until sacrifice. Glial fibrillary acidic protein (GFAP) was examined by Western blotting and immunohistochemistry. Levels of cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-κB) were measured by immunohistochemistry. IL-1β and TNF-α levels were tested with ELISA method.

Results

Levels of GFAP, COX- 2, NF-κB, IL-1β and TNF-α were all up-regulated after permanent BCCAO, which could be significantly inhibited by minocycline.

Conclusion

Minocycline could ameliorate the inflammation and oxidative stress in the hippocampus of the vascular cognitive impairment rat model.

摘要

目的

观察美满霉素(minocycline)对血管性认知功能损伤大鼠海马组织GFAP、 COX-2、 NF-κB、 IL-1β 和 TNF-α表达的影响, 探讨美满霉素对血管性认知功能损伤脑保护作用的机制。

方法

Wistar大鼠随机分为假手术组 (S组)、血管性认知功能损伤模型组(M组)和美满霉素治疗组(MT组)。 免疫组织化学法检测大鼠海马组织COX-2和 NF-κB的表达, 蛋白质印迹和免疫组织化学法检测大鼠海马组织GFAP的表达, ELISA法检测大鼠海马组织IL-1β和 TNF-α 的表达。

结果

MT 组GFAP、COX-2、 NF-κB、 IL-1β 和TNF-α 表达较M组均降低(P<0.01); MT 和M组 GFAP、COX-2、 NF-κB、 IL-1β 和TNF-α 表达均显著高于S 组(P<0.01)。

结论

美满霉素能降低血管性认知功能损伤大鼠海马组织中GFAP、 COX-2、 NF-κB、 IL-1β 和TNF-α 的表达, 抑制血管性认知功能损伤大鼠海马星型胶 质细胞活化和神经炎症, 发挥脑保护作用。

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Authors and Affiliations

  1. Department of Neurology, Lu’an People’s Hospital, the Fifth Clinical College, Anhui Medical University, Lu’an, 237005, China

    Zhi-You Cai  (蔡志友) & Ran Chen  (陈然)

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

    Yong Yan  (晏勇)

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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. & Chen, R. Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model. Neurosci. Bull. 26, 28–36 (2010). https://doi.org/10.1007/s12264-010-0818-2

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  • DOI: https://doi.org/10.1007/s12264-010-0818-2

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