摘要
目的:观察金钗石斛总生物碱对散发型老年痴呆动物脑内胰岛素信号的影响。方法:采用双侧侧脑室注射链脲佐菌素制备大鼠散发型老年痴呆模型,空白对照组大鼠侧脑室注射溶媒。术后动物分为:模型对照组、金钗石斛总生物碱20 mg/kg、40 mg/kg组,另设空白对照组、空白+总生物碱(40 mg/kg)组。治疗组大鼠灌胃相应剂量的总生物碱,空白对照和模型对照组大鼠灌胃等体积蒸馏水,每天1次,连续28 d。灌胃结束前6 d采用Morris水迷宫检测大鼠行为学功能;麻醉处死大鼠并收集大脑,HE染色观察海马神经元形态及数量,Western blot法检测海马胰岛素受体(IR)、胰岛素底物-1(IRS-1)、蛋白激酶B(Akt)的蛋白表达水平及磷酸化程度。结果:水迷宫结果提示,与空白对照组大鼠相比,模型对照组大鼠逃避潜伏期明显延长;与模型对照组相比,给予金钗石斛总生物碱后大鼠逃避潜伏期显著缩短(P<0.01)。HE染色发现模型对照组大鼠海马CA3区神经元层次减少、排列紊乱、细胞深染,且神经元密度下降;给予金钗石斛总生物碱后部分改善了神经元的形态并提高了神经元密度(P<0.01)。模型对照大鼠海马组织IR的磷酸化水平较空白对照组大鼠明显下调,而IRS和Akt的磷酸化水平则显著下调,给予金钗石斛总生物碱40 mg/kg后显著上调了IR磷酸化、下调了IRS和Akt的磷酸化水平(P<0.01)。结论:金钗石斛总生物碱能减轻链脲佐菌素所致痴呆大鼠学习记忆功能的损害,可能与调节脑内异常的IR/IRS-1/Akt通路中关键靶点的作用有关。
Objective: To observe the effect of Dendrobium nobile Lindl. alkaloids(Alkaloids) on the insulin signaling pathway in the brain of sporadic Alzheimer’s Disease(SAD) animal. Methods:Rats were injected with streptozotocin into the bilateral ventricles to establish SAD model, rats in the control group were injected with solvent. After modeling, rats were divided into 5 groups: the control group,the control + Alkaloids(40 mg/kg),the model group,the model +Alkaloids 20 mg/kg and 40 mg/kg groups. Rats were intragastrically administered with corresponding drugs or distilled water for 28 consecutive days. 6 days before the end of administration, Morris water maze was used to detect the behavioral ability of rats. After administration, rats were sacrificed under anesthesia condition and the brains were quickly collected. HE staining was used to observe the morphology and the quantity of hippocampal neurons. Western blot was used to detect the protein expressions and phosphorylation of insulin receptor(IR),the insulin substrate-1(IRS-1) and protein kinase B(Akt) in the hippocampus. Results:For Water maze results, compared with the control group, the escape latency of model rats was significantly increased. Compared with the model group,the escape latency in Alkaloids group was significantly shortened(P<0.01). HE staining showed that the decreased neuron density,disordered arrangement and deeply stained were found in hippocampal CA3 subfield of model rats. After treatment with Alkaloids, the neuron density was increased and the morphology of neuron was improved in CA3 subfield(P<0.01). Compared with the control group, the phosphorylation level of IR in hippocampus was significantly down regulated in the model group,while the phosphorylation level of IRS and Akt were significantly up regulated. After treatment, the phosphorylation level of IR was up regulated, the phosphorylated level of IRS and Akt was down regulated(P<0.01). Conclusion: Dendrobium nobile Lindl. alkaloids ameliorates the learning and memory impairment of streptozotocin-induced dementia rats, which may be related to regulating the key targets of abnormal IR/IRS-1/Akt signal pathway in the brain.
作者
李娟
李菲
龚其海
Li Juan;Li Fei;Gong Qihai(Department of Rheumatology,Chinese Medicine Hospital in Linyi City,Shandong Linyi 276000;Department of Pharmacology,Key Laboratory of Basic Pharmacology of Ministry of Education&Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Guizhou Zunyi 563000)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2020年第2期145-149,共5页
Pharmacology and Clinics of Chinese Materia Medica
基金
教育部创新团队(编号:IRT_17R113)
贵州省国际科技合作计划项目(黔科合外G字[2014]7011)。
关键词
金钗石斛总生物碱
胰岛素受体
胰岛素底物-1
链脲佐菌素
散发型老年痴呆
Dendrobium nobile Lindl.Alkaloids
insulin receptor
insulin receptor sudstrate-1
streptozotocin
sporadic Alzheimer’s Disease
