摘要
目的动态观察雷公藤红素对APPswe/PS1dE9双转基因阿尔茨海默病(alzheimers disease,AD)模型小鼠肝叶部分切除术后认知功能及海马内周期蛋白依赖性蛋白激酶5(cyclin-dependent kinase 5,Cdk5)和激动因子p25和p35表达的影响。方法 3月龄AD模型小鼠96只,随机均分为三组:手术组(S组),麻醉后行肝叶部分切除术;雷公藤红素组(C组),手术前3d上午腹腔注射雷公藤红素60μg/kg;二甲亚枫(DMSO)组(O组),手术前3d上午腹腔注射同体积的0.04%DMSO。三组随机抽取8只小鼠采用水迷宫连续训练5d并检测术后1、3、7、14d的学习记忆能力,余下小鼠分别于术后1、3、7、14d取标本,每次6只,检测海马内细胞Cdk5及激动因子p25、p35的表达。结果与C组比较,术后3、7和14dS和O组小鼠逃避潜伏期明显延长(P<0.05)、目的象限时间百分比明显降低(P<0.05);与C组比较,S和O组术后3、7、14d海马内Cdk5表达和术后1、3、7、14d海马内p25表达明显增高(P<0.01)。三组小鼠海马内p35表达差异无统计学意义。结论雷公藤红素可改善肝叶部分切除术后AD模型小鼠的认知功能的下降,其机制可能与Cdk5和p25蛋白表达下降有关。
Objective To investigate the impact of celastrol on cognitive function and the ex-pression of Cdk5/p25 in hippocampus in APPswe/PS1dE9 double transgenic mouse after partial hepa-tectomy.Methods Three-month-old APPswe/PS1dE9 double transgenic mice （n=96）were randomly divided into surgery group （partial hepatectomy,group S）,celastrol group （celastrol and partial hepa-tectomy,group C）and DMSO group （DMSO and partial hepatectomy,group O）.Eight mice were se-lected randomly in each group and were Morris-water maze trained for 5 continuous days.Their learn-ing and memory abilities were evaluated at 1,3,7 and 14 d after the surgery,respectively.For the remaining mice in each group,the hippocampus were collected and the changes of Cdk5,p35 and p25 in hippocampus were measured by western blot at the time 1,3,7,14 d after partial hepatectomy. Six mice were killed at each time for data collection.Results The average escape latency of group C was significantly shorter than those of groups S and O at 3,7 and 14 d after partial hepatectomy （P 〈0.05）.The percentages of time in target quadrant of groups S and O decreased significantly than that in group C （P 〈0.05）.Western blot showed the expression of Cdk5 in group C was significantly low-er than that in groups S and O at 3,7 and 14 d after partial hepatectomy （P 〈0.05）,and the same re-sult was also found in the expression of p25 at 1,3,7 and 14 d after partial hepatectomy （P 〈0.05）. There was no significant difference in the expression of p35 between each group.Conclusion Celas-trol can improve the learning and memory ability in APPswe/PS1dE9 the double transgenic mouse, with the mechanism may be related to the decrease of Cdk5 and p25 in hippocampus.
出处
《临床麻醉学杂志》
CAS
CSCD
北大核心
2014年第7期693-696,共4页
Journal of Clinical Anesthesiology
