2型糖尿病KKAy小鼠海马神经元存活信号转导途径的异常及APP17肽对其的改善作用  

Abnormal signal transduction pathway in hippocampal neuron of diabetic KKAy mice and the effect of APP17 peptide

作　　者：庄晓明[1] 姬志娟[2] 陈莉[3] 赵志炜[2] 安威[3] 盛树力[2] 

机构地区：[1]首都医科大学附属复兴医院内分泌科,北京100038 [2]首都医科大学宣武医院北京脑老化研究所多肽研究室,北京100053 [3]首都医科大学细胞生物教研室,北京100054

出　　处：《中国药理学通报》2004年第1期25-28,共4页Chinese Pharmacological Bulletin

基　　金：国家科技部"973"课题资助项目 NoG2 0 0 0 0 5 70 10

摘　　要：目的　观察APP17肽对 2型糖尿病KKAy小鼠大脑海马神经元一些信号转导蛋白表达的影响。方法　将KKAy小鼠分为正常对照组 (C组 )、糖尿病组 (DM组 )和APP17肽治疗组 (DM +APP17P组 )。APP17肽皮下注射 ,每周 3次 ,每次 8μg·kg-1。 12wk后将 3组小鼠颈部离断 ,处死 ,冰浴中快速分离海马组织 ,匀浆后 ,用于免疫沉淀并蛋白印迹检测 ,部分快速灌注固定做免疫组化染色和Tunel细胞染色。结果　DM组 pMAPK的表达低于C组和DM +APP17P ;CREB、pCREB、Bax、Bcl 2的表达 3组之间差异无显著性。结论　 2型糖尿病KKAy小鼠存在海马胰岛素信号转导通路的异常 ,主要表现为Ras途径和PI3 K两条途径的异常。这种信号转导途径的异常可通过神经元一定程度上的自我调节而改善 ,不出现凋亡状态 ;App17肽作为神经营养因子能激活海马神经元存活信号转导通路上游成分 。AIM To investigate the expressions of associated proteins of signaling transduction pathway in hippocampal nerve system of KKAy mouse with type 2 diabetes. To observe the effect of APP17 peptide on those signal transduction associated proteins. METHODS KKAy mice were divided into three groups named as normal control group (C), diabetic group (DM) and diabetic group treated with APP17 mer peptide (DM+APP17P). The mice in the last group were injected APP17 peptide subcutaneously at the dose of 8 μg·kg -1 three times a week for 12 weeks. All the mice were killed after twelve weeks. Homogenates were pepared from mice hippocampal tissue. Immunoprecipatation, Western Blot and immunohistochemical were used to analysis the proteins related to signal transduction pathyway. Tunnel assay was used to exam the apoptotic cell in hippocampus of KKAy mice. RESULTS The expression of phosphorylated MAPK(p MAPK) in DM group were diminished than DM+APP17P, while the expressions of CREB, p CREB, Bax and Bcl 2 showed no marked difference among the three groups. No positive Tunel cell was found in all groups. CONCLUSIONS Abnormal signal transduction pathway is present in hippocampal neuron of KKAy mice. The abnormality of signal transduction pathway included the abnormality of Ras and PI3 K pathway. Due to auto regulation of neurons in a certain extent, the abnormality of this signal transduction pathway may not lead to apoptosis. This abnormality of transduction pathway can be improved by APP17 peptide.

关 键 词：APP17肽 2型糖尿病 KKAY小鼠 信号转导通路 

分 类 号：R-332[医药卫生] R322.81