Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model
- PMID: 20101270
- PMCID: PMC5560381
- DOI: 10.1007/s12264-010-0818-2
Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model
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-kappaB) were measured by immunohistochemistry. IL-1beta and TNF-alpha levels were tested with ELISA method.
Results: Levels of GFAP, COX-2, NF-kappaB, IL-1beta and TNF-alpha 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.
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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