PI3K特异性抑制剂Wortmannin和APP17肽对SY5Y细胞胰岛素信号转导通路的作用  

Effect of Wortmannin and APP 17-mer peptide on insulin signal transduction pathway of SY5Y cells

作　　者：张景燕[1] 孟艳[1] 王蓉[1] 姬志娟[1] 盛树力[1] 

机构地区：[1]首都医科大学宣武医院中心实验室

出　　处：《中国糖尿病杂志》2008年第7期429-431,共3页Chinese Journal of Diabetes

基　　金：国家重点基础研究发展计划资助项目(973计划)血瘀证的生物学基础研究(2003CB517104);国家自然科学基金资助项目(30772288);北京市自然科学基金资助项目(7082043)

摘　　要：目的利用PI3K的特异性抑制剂Wortmannin阻断体外培养的人神经母细胞瘤株SY5Y细胞的存活信号转导通路,观察β淀粉样肽前体蛋白(APP)17肽对SY5Y细胞生长的影响及其作用机制。方法体外培养SY5Y细胞,分为对照组、Wortmannin组、APP17肽组、APP17肽+Wortmannin组、葡萄糖组、葡萄糖+APP17肽组、葡萄糖+Wortmannin+APP17肽组,观察各组细胞的噻唑蓝(MTT)代谢率、乳酸脱氢酶(LDH)漏出率、细胞轴突长度、胞体面积。结果(1)APP17肽可促进SY5Y细胞MTT代谢率升高、LDH漏出率降低、细胞轴突长度和胞体面积增加,但经Wortmannin作用后,其作用减弱。(2)APP17肽对高糖环境下的SY5Y细胞也有上述作用,且经Wortmannin作用后其作用减弱。结论APP17肽能通过激活胰岛素的PI3K信号转导通路发挥其神经保护作用。Objective To explore the mechanism of neurotrophic function of APP17-mer peptide. Methods The specific inhibitor of PI3 ＇ K Wortmannin were used to inhibit the signal transduction pathway of human neuroblasts SY5Y cells that were cultured in 11.5mmol/L glucose medium and the effect of APP 17-mer peptide on growth of these cells were observed. SY5Y cells were divided into seven groups： control, Wortmannin, APP 17-mer peptide, APP： 17-mer peptide＋ Wortmannin, 11.5mmol/L glucose, 11.5 mmol/L glucose ＋ APP 17-mer peptide, 11.5mmol/L glucose ＋ APP 17-mer peptide ＋ Wortmannin. There were 8-12 wells in each group. MTT metabolism,LDH leakage,length of cell axon and area of cell body were measured and analyzed. Results 1. The MTT metabolism of SYSY cells increased, LDH leakage decreased,length of axon and cell body area increased in APP 17-mer peptide group. However,above action weakened after treatment with Wortmannin. 2. The MTT metabolism of SY5Y cells decreased,LDH leakage increased,length of axon and cell body area decreased in SYSY cells of 11.5mmol/L glucose group. The APP 17-mer peptide could improve above changes caused by high concentration glucose. However, those were also weakened in the Wortmannin group. Conclusions APP 17-mer peptide exerts neurotrophic effects by activating PI3-K signal transduction pathway.

关 键 词：β淀粉样肽前体蛋白 胰岛素 WORTMANNIN 

分 类 号：R587.1[医药卫生—内分泌] R749.16[医药卫生—内科学]