Department of Neurology, Anhui Medical University, Lu'an 237005, China.
Neurosci Bull. 2010 Feb;26(1):28-36. doi: 10.1007/s12264-010-0818-2.
To study the neuroprotective mechanism of minocycline against vascular cognitive impairment after cerebral ischemia.
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.
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.
Minocycline could ameliorate the inflammation and oxidative stress in the hippocampus of the vascular cognitive impairment rat model.
研究米诺环素对脑缺血后血管性认知障碍的神经保护机制。
采用永久性双侧颈总动脉闭塞（BCCAO）建立血管性认知障碍大鼠模型。观察时间点分别为 BCCAO 后 4、8 和 16 周。动物随机分为假手术组（n = 6）、模型组（分为 3 组：BCCAO 后 4 周，n = 6；BCCAO 后 8 周，n = 6；BCCAO 后 16 周，n = 6）和米诺环素组（分为 3 组：BCCAO 后 4 周，n = 6；BCCAO 后 8 周，n = 6；BCCAO 后 16 周，n = 6）。BCCAO 后通过灌胃给予米诺环素，直至处死。通过 Western blot 和免疫组化检测胶质纤维酸性蛋白（GFAP）。通过免疫组化检测环氧化酶-2（COX-2）和核因子-kappaB（NF-kappaB）的水平。采用 ELISA 法检测白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的水平。
永久性 BCCAO 后，GFAP、COX-2、NF-kappaB、IL-1β和 TNF-α水平均升高，米诺环素可显著抑制其升高。
米诺环素可改善血管性认知障碍大鼠模型海马区的炎症和氧化应激。
