CAJ | 학술논문

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印迹法检测IGF-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、100 μmol/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(1.72±0.33)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＜0.0l),100 μmol/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.
목적 종수체각도탐토중추이도소양생장인자Ⅰ (IGF-Ⅰ)신호실조화아이자해묵병가능적분자발병궤제.방법 불동농도적Aβ1-42처리체외배양적원대해마신경세포,류식세포술감정세포조망비례,실시정량PCR화Western인적법검측IGF-Ⅰ수체적표체.결과 해마신경세포제7천발육성숙；경류식세포술검측,Aβ1-42 0、30、60、100 μmol/L각처리조적세포조망비례정농도의뢰성증고.PCR결과제시30(1.72±0.33)화60μmol/L(1.86±0.36)처리조적IGF-Ⅰ수체수평명현고우대조조(설위1)(P＜0.0l),100 μmol/L조(0.70±0.15)칙명현저우대조조(P＜0.05).Western 결과여PCR결과추세상사,30화60μmol/L처리조적단백수평위1.08 ±0.04,1.74±0.08 (P＜0.01),100μmol/L조위0.79±0.11 (P ＜0.05).결론 Aβ1-42유도대서해마세포IGF-Ⅰ수체적표체발생개변,가능위아이자해묵병발병적분자궤제지일.
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 O,30,60,100 μmol/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 ),100 μmol/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/Lprotein 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 Aβ1-42 induced altered expression of IGF- Ⅰ receptors in rat hippocampus cells,maybe one of the molecule mechanisms of Alzheimer disease.