淫羊藿次苷Ⅱ通过诱导自噬改善链脲佐菌素所致的大鼠学习记忆减退  

Icariside Ⅱ ameliorates streptozotocin-induced learning and memory impairments through inducing autophagy in rats

作　　者：邓媛媛[1] 李安霞[1] 尹彩霞[1] 龚其海[1] 

机构地区：[1]遵义医学院基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563099

出　　处：《中国新药与临床杂志》2017年第6期347-352,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：贵州省科技厅联合资金项目(黔科合LH字[2015]7533号);贵州省卫生计生委科学技术基金项目(gzwjkj2014-1-069);遵义市科技局遵义医学院联合资金项目(遵市科合社字[2016]29号)

摘　　要：目的探索淫羊藿次苷Ⅱ(ICSⅡ)对链脲佐菌素(STZ)所致大鼠学习记忆减退的作用及机制。方法雄性SD大鼠随机分为假手术组,模型组,ICSⅡ低、高剂量组(均n=10)。模型组和ICSⅡ组大鼠在第1日和第3日双侧侧脑室注射STZ 5μL(1.5 mg·kg^(-1))模拟散发性老年性痴呆,假手术组注入等体积柠檬酸缓冲液。第二次手术后开始给药,ICSⅡ低、高剂量组每日灌胃ICSⅡ3、10 mg·kg^(-1),假手术组和模型组给予等体积双蒸水,连续给药21 d。给药后第16日开始进行为期6 d的Morris水迷宫实验检测大鼠行为学功能。水迷宫实验结束后,通过Western blot实验技术检测大鼠海马组织中自噬基因Beclin 1、微管相关蛋白1轻链3(LC3)Ⅰ和LC3Ⅱ的蛋白表达以及β-淀粉样蛋白(Aβ1-42)的含量。结果水迷宫实验中模型组较假手术组大鼠的平均逃避潜伏期明显延长,穿越目标象限次数显著减少(P<0.05);海马组织中Aβ1-42的含量显著增加(P<0.05),Beclin 1表达明显减少(P<0.05),LC3-Ⅱ/LC3-I比值降低(P<0.05)。与模型组相比,ICSⅡ高剂量组大鼠逃避潜伏期缩短(P<0.05),穿越原平台象限次数增加(P<0.05);Aβ1-42的蛋白含量明显降低(P<0.05),LC3-Ⅱ/LC3-Ⅰ比值及Beclin 1蛋白表达显著增加(P<0.05)。结论自噬途径参与了STZ诱导的大鼠学习记忆减退;ICSⅡ具有抗侧脑室注射STZ诱导的认知功能损伤作用,其机制可能与诱导细胞自噬有关。AIM To explore the effects of icariside Ⅱ （ICS Ⅱ ） on streptozotocin-induced learning and memory deficits in rats. METHODS Male SD rats were randomly divided into sham group, model group, ICS Ⅱ low dose group and high-dose group （n = 10）. STZ-induced model animals were injected with STZ 5 p.L （ 1.5 mg·kg^-1） into the bilateral lateral at the first day and the third day, and the sham group was injected with volume- matched citrate buffer solution. The low and high dose ICS 11 -treated groups were intragastricly administered with ICS I1 3 mg·kg^-1·d^-1 and 10 mg·kg^-1·d^-1 after the second STZ injection for 21 consecutive days, while the sham and model were given an equal volume of solvent, instead. Morris water maze was used to detect the behavioural function of rats on 17th day to 21th day. Then animals were sacrificed, the expression of Beclin 1, microtubule-associated protein 1 light chain 3 （LC3）-I and LC3- 11 were examined by Western blot. RESULTS Compared with the sham group, the mean escape latency of space navigation test was increased （P 〈 0.05） and the number of crossing platform region of spatial exploring test was significantly reduced （P 〈 0.05） in the model group in Morris water maze test. Moreover, the content of Aβ1-42 in the hippocampus of the model group was significantly increased compare to the sham group （P 〈 0.05）, while the protein expression of Beclin 1 and the ratio of LC3- II/LC3-I were decreased （P 〈 0.05）. The mean escape latency were reduced in day 4 and day 5 （P 〈 0.05） and the number of crossing platform region were increased in the ICS Ⅱ high- dose group （P 〈 0.05）. In addition, the STZ-induced overexpression of Aβ1-42 was attenuated （P 〈 0.05） and the reduction in protein expressions of Beclin 1 and the ratio of LC3-Ⅱ/LC3-I were increased （P 〈 0.05） in the ICS 1/ high- dose group. CONCLUSION Autophagy pathway is involved in STZ-induced learning and memory impairment in rats. ICS Ⅱ attenuates cognitiv

关 键 词：淫羊藿次苷Ⅱ 链脲菌素 自噬 阿尔茨海默病 认知障碍 大鼠 

分 类 号：R971[医药卫生—药品]