摘要
目的探讨川芎嗪(tetramethylpyrazine,TMP)对慢性脑缺血小鼠认知功能障碍及海马星形胶质细胞胶质原纤维蛋白(glial fibrillary acidic protein,GFAP)表达的影响。方法采用改良双侧颈总动脉结扎术建立小鼠慢性脑缺血模型,经腹腔分别注射30和80 mg/kg的TMP注射液(即TMP低、高剂量组),每组10只,另设假手术组(不结扎),模型组和假手术组腹腔注射等量生理盐水。各组均在术后24 h开始给药,每日1次,连续8周。Morris水迷宫试验检测小鼠空间学习和记忆能力;黄嘌呤氧化酶法检测小鼠海马组织中的超氧化物歧化酶(superoxidedismutase,SOD)含量,硫代巴比妥酸(TBA)法检测丙二醛(malonaldehyde,MDA)含量,双抗体两步ELISA法检测肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)及白介素-1β(interleukin-1β,IL-1β)含量;免疫组织化学染色法及Western blot法检测小鼠海马CA1区GFAP的表达水平。结果与模型组比较,TMP低、高剂量组小鼠在Morris水迷宫定位航行试验中的逃避潜伏期和游泳路程均明显缩短(P<0.05),空间探索试验中穿越原平台的次数增多(P<0.05);小鼠海马组织中SOD含量明显增加(P<0.05),MDA、TNF-α及IL-1β含量明显降低(P<0.05);IOD值明显下降(P<0.05),GFAP表达水平明显下降(P<0.05)。结论 TMP可改善慢性脑缺血小鼠认知功能障碍,其机制可能是增强抗脂质氧化能力,抑制星形胶质细胞增生活化,减少GFAP的表达,减轻炎症反应,从而降低对海马组织的损害。
Objective To investigate the effect of tetramethylpyrazine （TMP） on cognitive impairment and expression of glial fibrillary acidic protein （GFAP） in hippocampal astrocytes of mice with chronic cerebral ischemia. Methods The mouse model of chronic cerebral ischemia was established by modified bilateral common carotid artery ligation （2VO）. The mice in two test groups were injected i. p. with TMP at low （30 mg/ kg） and high （80 mg/ kg） dosages respectively, 10 for each, while those in model control and normal （sham operation） control groups with an equal volume of physiological saline, 24 h after operation, once a day for 8 weeks. The spatial learning capacity and cognitive function of mice were evaluated by Morris water maze. The superoxidedismutase （SOD） content in hippocampus of mice was determined by xanthine oxidase test, while the malonaldehyde （MDA） content by thiobarbituric acid test, and the tumor necrosis factor （TNF）-α and interleukin-lβ （IL-1β） contents by double antibody ELISA. The expression level of GFAP in hippocampal CAI region of mice was determined by immunohistochemical staining and Western blot. Results Compared with those in model control group, the escape latency and swimming distance of mice injected with TMP at low and high dosages in water maze localization experiment were shortened significantly （P 〈 0. 05 ）, the times of crossing the original platform in space exploration experiment increased significantly （P 〈 0. 05）, and the SOD content in hippocampus increased significantly （P 〈 0. 05 ）. However, the MDA, TNF-α and IL-1 β contents, the IOD value and the GFAP expression level decreased significantly （each P 〈 0. 05）. Conclusion TMP improved the cognitive impairment of mice with chronic cerebral ischemia by a possible mechanism of enhancing the anti-lipid oxidation ability, inhibiting the proliferation and activation of astrocytes, decreasing the expression of GFAP, relieving the inflammatory response and reducing the
出处
《中国生物制品学杂志》
CAS
CSCD
2018年第2期150-154,159,共6页
Chinese Journal of Biologicals
基金
重庆市教委项目(KJ1725384)
重庆三峡医专校级苗圃工程自然科学(2016mpxz17)
关键词
慢性脑缺血
脂质氧化
星型胶质细胞
川芎嗪
海马
Chronic cerebral ischemia
Lipid oxidation
Astrocytes
Tetramethylpyrazine （TMP）
Hippocampus
