摘要
目的观察知母皂苷(SAaB)是否对脂多糖(LPS)引起的大鼠学习记忆障碍和炎症反应有改善作用。方法大鼠随机分为对照组、LPS损伤组、LPS+SAaB(20、40mg·kg-1)组。对照组和LPS损伤组大鼠灌胃给予0.2%的二甲基亚砜,SAaB组大鼠灌胃给予SAaB。连续给药7d后,左侧脑室内单次注射LPS30μg/只大鼠,注射量为5μl,正常对照组大鼠注射等量的生理盐水。脑室注射后d2进行大鼠Morris水迷宫实验,连续6d,训练期间继续给药。水迷宫实验结束后,Nissl染色观察海马CA1区锥体神经元改变;白细胞介素-1β(IL-1β)分别与integrinαM和胶质原纤维酸性蛋白(GFAP)双重免疫荧光染色观察IL-1β表达部位;Westernblot检测海马IL-1β、诱导型一氧化氮合酶(iNOS)的表达水平。结果 SAaB(40mg·kg-1·d-1)能明显改善LPS所致大鼠学习记忆能力损伤,表现在明显缩短大鼠的逃避潜伏期,增加大鼠在原平台象限的游泳时间占总游泳时间的百分比;海马CA1区锥体神经元损伤较LPS组明显减轻,对抗LPS引起的IL-1β及iNOS的蛋白表达水平增加;激光共聚焦实验结果显示IL-1β主要在小胶质细胞表达,少量在星形胶质细胞表达。结论 SAaB能改善LPS引起的大鼠学习记忆障碍,抑制其海马的炎症反应。
Aim To observe the effects and mechanisms of SAaB on LPS-induced learning and memory disorders and inflammatory reaction in rat hippocampus.Methods The rats were randomly divided into normal group,LPS group and LPS＋SAaB（20 and 40 mg·kg -1 ） group.On d 1,the rats of control,model and SAaB groups were given 0.2%dmso and SAaB ig,respectively.On d 2,single dose LPS（5μl） was given via intracerebroventricular injection to model and SAaB groups（after SAaB given） .Then,the rats of SAaB were given SAaB for 6 d.Morris water maze was used to measure learning and memory performance.Nissl staining was used to determine the morphology of pyramidal neurons in hippocmpal CA1 regions.The levels of inducible nitric oxide synthase（iNOS） and interlukin（IL） -1βwere determined by Western blot.Immunohistochemistry and double labeling immunofluorescence combined with laser scanning confocal microscope were used to investigate the expression of GFAP and OX-42 protein in hippocampal CA1 areas.Results Intracerebroventricular injection of LPS in rats resulted in learning and memory impairments shown by longer escape latency and decreased percentage of time spent in the target quadrant.These behavioral dysfunctions were accompanied by microglia activation and infiltration,increased IL-1βproduction and elevated iNOS level,the loss of pyramidal neurons in hippocampal CA1 regions. Oral administration of SAaB（40 mg·kg-1·d-1） markedly improved the learning and memory performance,attenuated pyramidal neurons damage,and reversed the LPS-induced increases in IL-1βand iNOS activation.Conclusion SAaB can attenuate the learning and memory impairment induced by LPS,which maybe related to its inhibitory effect on inflammatory response in hippocampus.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2010年第10期1362-1366,共5页
Chinese Pharmacological Bulletin
基金
辽宁省教育厅创新团队资助项目(NoLT2010064)
辽宁医学院院内资助课题(NoY2010Z003)
