美满霉素抑制血管性痴呆大鼠脑组织NF-κB、GFAP与IL-1β的表达
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国家民政部中国老年学学会资助课题(2007-18-3-05); 重庆医科大学博士课题基金(2006010068).


Minocycline inhibits expression of NF-κB, GFAP and IL-1β in brain of rats with vascular dementia
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Supported by Subject of Gerontology Association of China(2007-18-3-05) and Doctoral Project of Chongqing Medical University(2006010068).

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    摘要:

    目的:观察美满霉素(minocycline)对血管性痴呆大鼠脑组织核因子κB (NF-κB)、星形胶质细胞标志物GFAP和炎症因子IL-1β表达的影响,探讨美满霉素对血管性痴呆脑保护作用的机制。方法:双侧颈总动脉结扎法建立血管性痴呆大鼠动物模型。随机分为假手术组,4、8、16周模型组,美满霉素治疗4、8、16周模型组。穿梭箱实验、Morris水迷宫实验检测认知行为学改变,ELISA法、蛋白质免疫印迹法和免疫组织化学法检测GFAP,ELISA法和免疫组织化学法检测NF-κB,ELISA法检测IL-1β。结果: 美满霉素可以显著改善血管性痴呆的行为学症状,提高学习记忆力和反应能力。模型组和美满霉素治疗组NF-κB、GFAP与IL-1β表达均较假手术组显著增高(P<0.01),但美满霉素治疗组三者表达较模型组明显降低(P<0.01)。结论:美满霉素可能通过降低血管性痴呆大鼠脑组织NF-κB、GFAP与IL-1β的表达,抑制星形胶质细胞激活和脑内炎症反应,发挥脑保护作用。

    Abstract:

    Objective:To observe the influence of minocycline on expression of NF-κB, GFAP, and IL-1β in rats with vascular dementia,so as to study the neuroprotective mechanism of minocycline for vascular dementia.Methods: An animal model of vascular dementia was established by chronic bilateral common carotid artery occlusion (BCCAO). Animals were randomly divided into sham-operation group(S), 4-week model group (M4), 8-week model group (M8), 16-week model group (M16), 4-week model + Minocycline group (T4), 8-week model+Minocycline group (T8), and 16-week model+Minocycline group (T16). The behaviors of animals were tested with Morris water maze and shuttle box task. Expression of NF-κB and GFAP was measured by enzyme linked immunosorbent assay (ELISA), immunohistochemistry and Western blotting,and IL-1β by ELISA.Results: Minocycline greatly improved the behaviors of mice with vascular dementia, and promoted the learning, memory and responding abilities. The expression of NF-κB, GFAP and IL-1β in all the model groups and Minocycline treatment groups were significantly higher than that in the sham-operation group (P<0.01); and those of Minocycline treatment groups were significantly lower than the corresponding model groups (P<0.01).Conclusion: Minocycline can decrease the expression of NF-κB, GFAP, and IL-1β in the brain of rats with vascular dementia, and protect brain by inhibiting the activation of astrocytes and neuroinflammation.

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  • 收稿日期:2008-03-26
  • 最后修改日期:2008-07-03
  • 录用日期:2008-09-18
  • 在线发布日期: 2008-10-08
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