微小RNA-206促进神经细胞凋亡参与阿尔茨海默病的机制研究  

Mechanism of miR-206in promoting neuronal apoptosis and participating in AD

作　　者：林晓光[1] 张雪玲[1] 王黎明[1] 刘芹芹 Lin Xiaoguang;Zhang Xueling;Wang Liming;Liu Qinqin(Department of Neurology,Suqian People’s Hospital,Nanjing Gulou Hospital Group,Suqian 223800,Jiangsu Province,China)

机构地区：[1]南京鼓楼医院集团宿迁市人民医院神经内科,223800

出　　处：《中华老年心脑血管病杂志》2020年第10期1090-1094,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：宿迁市科技局科研项目(S201714)。

摘　　要：目的探究微小RNA-206(miR-206)通过调节脑源性神经营养因子(BDNF)及磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)通路,促进神经元凋亡参与阿尔茨海默病(AD)的机制。方法将大鼠海马神经细胞分为对照组、AD组、miR-206抑制剂组(抑制剂组)、抑制剂+siBDNF组和siBDNF组(n=3),除对照组外,其他4组建立AD模型,抑制剂组和抑制剂+siBDNF组通过转染miR-206抑制剂质粒以抑制miR-206,抑制剂+siBDNF组和siBDNF组转染BDNF质粒沉默BDNF。在转染48h后,检测miR-206、BDNF mRNA和蛋白表达水平。结果AD组miR-206、细胞凋亡率、Thr231/tau-5及Ser404/tau-5水平明显高于对照组和抑制剂组,BDNF mRNA和蛋白表达、细胞活力、磷酸化PI3K/PI3K及磷酸化Akt/Akt表达明显明显低于对照组和抑制剂组(P<0.05)。siBDNF组细胞活力、BDNF mRNA和蛋白表达、磷酸化PI3K/PI3K、磷酸化Akt/Akt表达明显低于AD组,miR-206、细胞凋亡率、Thr231/tau-5、Ser404/tau-5蛋白表达明显高于AD组(P<0.05)。抑制剂+siBDNF组miR-206、细胞凋亡率、Thr231/tau-5和Ser404/tau-5蛋白水平明显高于抑制剂组[(1.79±0.18)vs(1.20±0.14),(14.37±1.72)%vs(6.84±0.48)%,(1.40±0.15)vs(0.89±0.09),(2.45±0.26)vs(1.12±0.12),P<0.05],细胞活力、BDNF mRNA和蛋白表达、磷酸化PI3K/PI3K和磷酸化Akt/Akt表达明显明显低于抑制剂组(P<0.05)。结论下调miR-206表达,会通过促进BNDF的水平激活PI3K/Akt通路,并提高AD模型细胞活力,抑制凋亡,这可能是治疗AD的新思路。Objective To study the mechanism of miR-206in promoting neuronal apoptosis and participating in AD by regulating BDNF and PI3K/Akt pathway.Methods Hippocampal nerve cells of rats were divided into control group,AD group,miR-206inhibitor group,miR-206inhibitor+siBDNF group and siBDNF group.A rat AD model was established for AD group,miR-206 inhibitor group,miR-206inhibitor+siBDNF group and siBDNF group.Forty-eight hours after the miR-206in miR-206inhibitor group and miR-206inhibitor+siBDNF group was inhibited by transfecting the miR-206inhibitor plasmids and the silent BDNF in miR-206inhibitor+siBDNF group and siBDNF group was transfected by the BDNF plasmids and the expressions of miR-206 and BDNF mRNA and protein were detected.Results The cell apoptosis rate and expression levels of miR-206,Thr231/tau-5,Ser404/tau-5were significantly higher while the cell viability and expression levels of BDNF mRNA and protein,p-PI3K/PI3Kand p-Akt/Akt were significantly lower in AD group than in control group and miR-206inhibitor group(P<0.05).The cell viability and expression levels of BDNF mRNA and protein,p-PI3K/PI3Kand p-Akt/Akt were significantly lower while the cell apoptosis rate and expression levels of miR-206,Thr231/tau-5and Ser404/tau-5were significantly higher in siBDNF group than in AD group(P<0.05).The cell apoptosis rate and expression levels of miR-206,Thr231/tau-5and Ser404/tau-5were significantly higher(1.79±0.18 vs 1.20±0.14,14.37%±1.72%vs6.84%±0.48%,1.40±0.15 vs 0.89±0.09,2.45±0.26 vs 1.12±0.12,P<0.05)while the cell viability and expression levels of BDNF mRNA and protein,p-PI3K/PI3Kand p-Akt/Akt were significantly lower in miR-206inhibitor+siBDNF group than in miR-206inhibitor group(P<0.05).Conclusion Down-regulated miR-206expression activates the PI3K/Akt pathway by upregulating the BNDF expression,improvs the cell viability and inhibits the cell apoptosis in AD model,which may be a new approach to the treatment of AD.

关 键 词：脑源性神经营养因子 阿尔茨海默病 淀粉样β肽类 细胞凋亡 

分 类 号：R749.16[医药卫生—神经病学与精神病学]