摘要
目的探讨金钗石斛生物总碱(DNLA)对脂多糖(LPS)诱导的大鼠学习记忆功能减退的改善作用及可能的作用机制。方法成年雄性SD大鼠经Morris水迷宫训练合格后,随机分为模型组和假手术组。模型组大鼠左侧脑室微量注射LPS(10.gL-1)5μL后分为LPS,LPS+布洛芬(Ibu,40 m.gkg-1),LPS+DNLA(20,40和80 mg.kg-1)组,假手术组左侧脑室注射5μL生理盐水。大鼠清醒后ig给予Ibu或DNLA,每天1次,连续14 d。用Morris水迷宫检测大鼠空间学习记忆能力;HE染色观察海马神经元形态改变;免疫组织化学法检测海马淀粉样β蛋白片段1-42(Aβ1-42)含量;实时荧光定量PCR检测海马半胱氨酸天冬氨酸蛋白酶(caspase)3/8 mRNA表达水平。结果侧脑室注射LPS后,大鼠水迷宫逃避潜伏期及搜索距离明显延长,海马出现神经元凋亡和坏死改变。Ibu和DNLA均能明显缩短模型大鼠水迷宫逃避潜伏期和搜索距离,减轻神经元凋亡和坏死,降低海马Aβ1-42含量和caspase 3/8 mRNA表达水平。结论DNLA可改善LPS诱导的大鼠学习记忆功能减退,其机制可能与降低海马caspase 3/8 mRNA表达、减少Aβ1-42产生有关。
AIM To explore the protective effect of Dendrobium nobile Lindl. alkaloids （DNLA） on the learning and memory deficit in rats induced by lipopolysaccharides （LPS）, and its possible underlying mechanisms. METHODS After trained by Morris water maze method, the qualified adult male SD rats were randomly divided into sham group and model group. The rat model was induced with slow microinjection of LPS （ 10 g· L^-1 ） 5μL into left lateral cerebral ventricles, and then divided into LPS, LPS ＋ ibuprofen （40 mg·kg^-1 ） and LPS ＋ DNLA （ 20, 40 and 80 mg·kg^-1） subgroups. The rats in sham group were microinjected with normal saline 5μL. After regaining consciousness the sober rats were given （ig） ibuprofen and DNLA, respectively, once daily for 14 d. The spatial learning and memory abilities were tested by Morris water maze. The morphological changes in hippocampal neurons were observed with HE staining under the optical microscope. The content of amyloid beta-protein fragment 1 -42 （ Aβ1 -42 ） in the hippocampus was examined by immunohis- tochemical analysis, and the expressions of caspases 3/8 mRNA were deteeted by real-time RT-PCR, respectively. RESULTS Injection of LPS to lateral cerebral ventricles evidently prolonged the escape latency and searching dis- tance of rats in Morris water maze, and impaired the hippocampal neurons with apoptosis and necrosis. However, ibuprofen and DNLA could markedly ameliorate the rat learning and memory deficit, attenuate the neuron apoptosis and necrosis, decrease the Aβ1-42 content and down-regulate the expressions of caspases 3/8 mRNA in the hippoeampus. CONCLUSION DNLA can attenuate cognitive deficits in rats induced by LPS, which may be related with the down-regulation of expressions of caspases 3/8 mRNA and the decrease of Aβ1-42 in the hippocampus.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2008年第6期406-411,共6页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金(30660208)
贵州省委组织部特助基金(C-277)
贵州省省长基金项目(C-262)~~
关键词
金钗石斛
生物碱
脂多糖
淀粉样Β蛋白
学习
记忆
Dendrobium nobile Lindl.
alka-loid
lipopolysaccharides
amyloid beta-pro-tein
learning
memory
