二苯乙烯苷对APP/PS1/Tau三转基因痴呆小鼠JNK和PP2B的调控作用研究
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篇名: 二苯乙烯苷对APP/PS1/Tau三转基因痴呆小鼠JNK和PP2B的调控作用研究
TITLE: Regulatory Effects of Stilbene Glucoside on JNK and PP 2B in APP/PS1/Tau Transgenic Dementia Mice
摘要: 目的:研究二苯乙烯苷(TSG)对APP/PS1/Tau三转基因痴呆(3×Tg-AD)小鼠c-Jun氨基末端激酶(JNK)、钙调神经磷酸酶(PP2B)的调控作用,探索该药抗阿尔茨海默病(AD)的可能机制。方法:将45只雄性3×Tg-AD小鼠随机分为模型组、阳性对照组(石杉碱甲,0.15mg/kg)和TSG低、中、高剂量组(0.033、0.1、0.3g/kg),每组9只;另取9只正常雄性C57BL/6J小鼠作为正常对照组。各给药组小鼠灌胃相应药物,每天给药1次,连续给药60d;正常对照组和模型组小鼠灌胃等量生理盐水。给药结束后,通过Morris水迷宫实验测定各组小鼠的空间学习记忆能力,采用尼氏染色法观察小鼠大脑皮层和海马部位尼氏小体变化情况,并分别采用实时荧光定量-聚合酶链式反应法和Westernblotting法检测小鼠脑组织中JNK、PP2B的mRNA及蛋白表达情况。结果:与正常对照组比较,模型组小鼠逃避潜伏期显著延长(P<0.01),原平台象限停留时间显著缩短(P<0.01),穿越平台次数显著减少(P<0.01);脑皮层和海马部位尼氏小体数量显著减少、着色浅;脑组织中JNKmRNA及其蛋白的相对表达量显著升高(P<0.01),PP2BmRNA及其蛋白的相对表达量显著降低(P<0.01)。与模型组比较,阳性对照组和TSG各剂量组小鼠逃避潜伏期显著缩短(P<0.01),原平台象限停留时间显著延长(P<0.01);穿越平台次数显著增加(P<0.01);脑皮质和海马部位尼氏小体数量显著增加、着色深;脑组织中JNK蛋白的相对表达量显著降低(P<0.05或P<0.01),PP2BmRNA及其蛋白的相对表达量显著升高(P<0.01),且TSG高剂量组小鼠脑组织中JNKmRNA的相对表达量显著降低(P<0.05)。结论:TSG对3×Tg-AD小鼠的学习记忆能力及神经元损伤有一定改善作用,其机制可能与下调蛋白激酶JNK的转录和表达、上调蛋白磷酸酶PP2B的转录和表达有关。
ABSTRACT: OBJECTIVE:To study the regulatory effects of stilbene glucosid e(TSG)on c-Jun N-terminal kinase (JNK)and protein phosphortase 2B(PP2B)in APP/PS1/Tau transgenic dementia (3×Tg-AD)mice,and to explore its potential mechanism of anti-Alzheimer’s disease (AD). METHODS :Totally 45 male 3×Tg-AD mice were randomly divided into model group ,positive control group (huperzine A ,0.15 mg/kg),TSG low-dose ,medium-dose and high-dose groups (0.033,0.1,0.3 g/kg),with 9 mice in each group. Another 9 normal male C 57BL/6J mice were included into normal control group. Administration groups were given relevant medicine intragastrically ,once a day ,for consecutive 60 d. Normal control group and model group were given constant volume of normal saline intragastrically. After medication ,Morris water maze experiment was used to test the spatial learning and memory ability of mice in each group ;Nissl staining was used to observe the changes of Nissl bodies in cerebral cortex and hippocampus ;mRNA and protein expressions of JNK and PP 2B were detected by qRT-PCR and Western blotting assay. RESULTS:Compared with normal control group ,the escape latency was significantly prolonged (P<0.01),the retention time of the original platform quadrant was significantly shortened (P< and the times of crossing the platform was significantly reduced in model group (P<0.01);the number of Nissl bodies in cerebral cortex and hippocampus was significantly 729011126@qq.com reduced,the staining was slight ;the relative expressions of JNK mRNA and protein were significantly increased (P< 0.01),and the relative expressi ons of PP 2B mRNA and protein were significantly decreased (P<0.01). Compared with model group ,the escape latency was significantly shortened in positive control group and TSG groups (P<0.01);the retention time of the original platform quadrant was significantly prolonged (P<0.01);the times of crossing the platform was significantly increased (P<0.01);the number of Nissl bodies in cerebral cortex and hippocampus was increased significantly ,the staining was heavy ;the relative expression of JNK protein was significantly decreased(P<0.05 or P<0.01),the relative expressions of PP 2B mRNA and protein were significantly increased (P<0.01), while the relative expression of JNK mRNA was significantly decreased in TSG high-dose group (P<0.05). CONCLUSIONS :TSG can improve the learning and memory ability and neuronal damage of 3 × Tg-AD mice. The mechanism may be related to down-regulating the transcription and expression of protein kinase JNK ,up-regulating the transcription and expression of protein phosphatase PP 2B.
期刊: 2020年第31卷第19期
作者: 吴文雪,苏彦兆,刘超宇,谭俊杰,李振中,黄健,朱晓莹,廖艳花,黄忠仕
AUTHORS: WU Wenxue,SU Yanzhao, LIU Chaoyu,TAN Junjie,LI Zhenzhong,HUANG Jian,ZHU Xiaoying,LIAO Yanhua,HUANG Zhongshi
关键字: 阿尔茨海默病;二苯乙烯苷;APP/PS1/Tau三转基因痴呆小鼠;c-Jun氨基末端激酶;钙调神经磷酸酶
KEYWORDS: Alzheimer’s disease ;Stilbene glucoside ;APP/PS1/Tau transgenic dementia mice ;c-Jun N-terminal kinase ;
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