阿尔茨海默病胰岛素样生长因子Ⅰ受体与β淀粉样蛋白的相关性分析

Study of the correlation about IGF, Ⅰ receptor and β-amyloid in Alzheimer＇s disease

目的从受体角度探讨中枢胰岛素样生长因子Ⅰ（IGF—Ⅰ）信号失调和阿尔茨海默病可能的分子发病机制。方法不同浓度的Aβ1-42。处理体外培养的原代海马神经细胞，流式细胞术鉴定细胞凋亡比例，实时定量PCR和Western印迹法检钡0IGF—Ⅰ受体的表达。结果海马神经细胞第7天发育成熟；经流式细胞术检测，Aβ1-42 0、30、60、100μmoL／L各处理组的细胞凋亡比例呈浓度依赖性增高。PCR结果提示30（1．72β0．33）和60μmol／L（1．86±0．36）处理组的IGF—Ⅰ受体水平明显高于对照组（设为1）（P〈0．01），100txmol／L组（0．70±0．15）则明显低于对照组（P〈0．05）。Western结果与PCR结果趋势相似，30和60μmol／L处理组的蛋白水平为1．08±0．04，1．74±0．08（P〈0．01），100μmol／L组为0．79±0．11（P〈0．05）。结论Aβ1-42诱导大鼠海马细胞IGF—I受体的表达发生改变，可能为阿尔茨海默病发病的分子机制之一。

Objective To detect the expression of IGF- I receptor in the hippocampus neuron of rat treated by Aβ1-42, and thus from the receptor level explore the disorder of central nervous insulin signaling and the possible molecular mechanism of Alzheimer disease. Methods Cultured primary hippocampus neurons were treated with different concentrations of Aβ1-42, apoptosis rate was detected by flow cytometry, real-time quantitative PCR and Western blot were used to detect IGF-I receptor expression. Results Primary cultured cells mature in 7th days; after detected by flow cytometry, early apoptosis rate in Aβ1-42 0, 30,60,100 p,mol/L groups showed a concentration-dependent increase. PCR results showed that, in 30 （ 1.72±0. 33 ） and 60 μmol/L （ 1.86± 0. 36 ） treatment groups levels of the IGF- I receptor gene were significantly higher than the control group （regarded as 1 ） （P 〈0. 01 ）, 100μmol/L group （0. 70± 0. 15 ） was significantly lower than the control group （ P 〈 0. 05 ）. Results of Western blot showed 30 and 60 μmol/L protein level of the treatment groups are 1.08 - 0. 04, 1.74 ±0. 08 （P 〈 0. 01 ） and 100 μmol/L group was 0. 79 ± 0. 11 （ P 〈 0. 05 ）, which had same trend with PCR. Conclusions A[3142 induced altered expression of IGF- Ⅰ receptors in rat hippocampus cells, maybe one of the molecule mechanisms of Alzheimer disease.