腹腔内注射脂多糖对大鼠黑质多巴胺能神经元和小胶质细胞形态学影响及炎性因子变化

doi:10.3969/j.issn.1006-7795.2015.06.010

首都医科大学学报 ›› 2015, Vol. 36 ›› Issue (6): 887-894.doi: 10.3969/j.issn.1006-7795.2015.06.010

• 神经系统疾病的基础研究 • 上一篇下一篇

腹腔内注射脂多糖对大鼠黑质多巴胺能神经元和小胶质细胞形态学影响及炎性因子变化

白丽娟¹, 任艳², 罗晓光², 姜新¹, 陈晓虹¹

1. 辽宁省人民医院神经内科, 沈阳 110016;
2. 中国医科大学附属第一医院神经内科, 沈阳 110001

收稿日期:2015-10-10 出版日期:2015-12-21 发布日期:2015-12-18
通讯作者: 白丽娟 E-mail:blj_0510@sina.com
基金资助:
辽宁省临床能力建设项目(LNCCC-B02-2015)。

Morphological and inflammatory factor changes of substantia nigra dopaminergic neurons and microglial cells after intraperitoneal injection of lipopolysaccharide in rat

Bai Lijuan¹, Ren Yan², Luo Xiaoguang², Jiang Xin¹, Chen Xiaohong¹

1. Department of Neurology, The People's Hospital of Liaoning Province, Shenyang 110016, China;
2. Department of Neurology, The First Hospital of China Medical University, Shenyang 110001, China

Received:2015-10-10 Online:2015-12-21 Published:2015-12-18
Supported by:
This study was supported by Clinical Ability Construction Program of Liaoning Province(LNCCC-B02-2015).

摘要/Abstract

摘要： 目的观察腹腔注射脂多糖(lipopolysaccharide,LPS)后,大鼠黑质多巴胺能神经元和小胶质细胞形态学变化及炎性因子的变化。方法健康2月龄、12月龄斯普雷格-道利(Sprague-Dawley,SD)大鼠经腹腔注射LPS(1 mg/kg)后,分别于6 h,12 h,24 h,48 h,1 周处死,用链霉菌抗生物素蛋白-过氧化物酶连结(streptavidin-peroxidase,SP)法进行抗酪氨酸羟化酶(tyrosine hydroxylase,TH)和抗钙离子结合蛋白1(ionized calcium binding adapter molecule 1,Iba-1)免疫组织化学染色,观察不同时间点脑黑质多巴胺能神经元阳性存活率及黑质小胶质细胞的激活情况。酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)法分别检测相应时间点血及脑脊液中肿瘤坏死因子α(tumor necrosis factor α,TNF-α)、白细胞介素6(interleukin 6,IL-6)及白细胞介素1β(interleukin 1β,IL-1β)的变化。结果腹腔注射LPS(1 mg/kg)后,老龄组大鼠小胶质细胞呈明显激活改变,且早于青年组小胶质细胞的高峰;各组小胶质细胞的激活早于多巴胺能神经元的损毁;老年组脑脊液中各种炎性因子水平高于青年组。结论老化因素与外周炎性介质诱发的中枢神经系统(central nervous system,CNS)炎性反应有关。

关键词: 小胶质细胞, 脂多糖, 多巴胺能神经元, 脑脊液, 肿瘤坏死因-子α, 白细胞介素6, 白细胞介素1β

Abstract: Objective To observe the morphological change of dopaminergic neurons and microglia after intraperitoneal injection of lipopolysaccharide(LPS). Methods Healthy two-month- and one-year-old SD rats were intraperitoneally injected with LPS(1 mg/kg) at 6 h, 12 h, 24 h, 48 h, and 1 w, respectively. Anti tyrosine hydroxylase(TH) and anti ionized calcium binding adapter molecule 1(Iba-1) immunohistochemial staining was utilized to observe TH positive neurons and activity of microglia in substantia nigra. The level of tumor necrosis factor α(TNF-α), interleukin 6(IL-6) and interleukin 1β(IL-1β) in blood and cerebrospinal fluid were detected by enzyme-linked immunosorbent assay(ELISA). Results Microglia of one-year-old SD rats were activated more significantly, and reached the peak earlier than the young group. The activation of microglia was earlier than the damage of dopaminergic neuron in each non-control group. The level of inflammatory factors in aged group was higher than that in the young group in cerebrospinal fluid. Conclusion Aging factors are related with CNS inflammatory reaction which is induced by the peripheral inflammatory media.

Key words: microglial cells, lipopolysaccharide(LPS), dopaminergic neuron, cerebrospinal fluid, tumor necrosis factor α(TNF-α), interleukin 6(IL-6), interleukin 1β(IL-1β)

中图分类号:

R742.5

白丽娟, 任艳, 罗晓光, 姜新, 陈晓虹. 腹腔内注射脂多糖对大鼠黑质多巴胺能神经元和小胶质细胞形态学影响及炎性因子变化[J]. 首都医科大学学报, 2015, 36(6): 887-894.

Bai Lijuan, Ren Yan, Luo Xiaoguang, Jiang Xin, Chen Xiaohong. Morphological and inflammatory factor changes of substantia nigra dopaminergic neurons and microglial cells after intraperitoneal injection of lipopolysaccharide in rat[J]. Journal of Capital Medical University, 2015, 36(6): 887-894.

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腹腔内注射脂多糖对大鼠黑质多巴胺能神经元和小胶质细胞形态学影响及炎性因子变化

Morphological and inflammatory factor changes of substantia nigra dopaminergic neurons and microglial cells after intraperitoneal injection of lipopolysaccharide in rat

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