Anle138b对oAβ_(1-42)诱导海马神经元突触毒性作用影响  

EFFECT OF ANLE138B ON SYNAPTIC TOXICITY OF HIPPOCAMPAL NEURONS INDUCED BY Aβ1-42 OLIGOMER

作　　者：孙琳[1] 王炳超[1] 朱天立 SUN Lin;WANG Bingchao;ZHU Tianli(Department of Physiology,School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院生理学教研室,山东青岛266071

出　　处：《青岛大学学报（医学版）》2023年第4期518-521,共4页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金面上项目(81771437)。

摘　　要：目的探究Anle138b对慢性β淀粉样蛋白寡聚体1-42(oAβ_(1-42))诱导的海马神经元突触毒性作用影响。方法培养原代海马神经元细胞,细胞发育成熟后分为对照组(不进行任何处理)、oAβ_(1-42)组(100 nmol/L oAβ_(1-42)处理7 d)、Anle138b组(50 nmol/L Anle138b处理2 d)、oAβ_(1-42)+Anle138b组(100 nmol/L oAβ_(1-42)+50 nmol/L Anle138b共处理7 d)、oAβ_(1-42)+Anle138b 2 d组(100 nmol/L oAβ_(1-42)处理7 d,在oAβ_(1-42)处理的最后2 d加用50 nmol/L Anle138b)。各组处理结束后,应用单细胞膜片钳技术检测自发性兴奋性突触后电流(sEPSCs)的幅值、频率、半衰减时间。结果各组海马神经元细胞sEPSCs幅值、半衰减时间比较差异无统计学意义(F=2.215、1.043,P>0.05)。各组sEPSCs频率比较差异有统计学意义(F=15.490,P<0.001),两两比较显示,oAβ_(1-42)组的sEPSCs频率较对照组明显增加(q=6.507,P<0.001),oAβ_(1-42)+Anle138b组和oAβ_(1-42)+Anle138b 2 d组的sEPSCs频率较oAβ_(1-42)组明显降低(q=9.517、9.471,P<0.001),其他组间比较差异均无统计学意义(P>0.05)。结论Anle138b不仅可以预防慢性oAβ_(1-42)诱导的海马神经元细胞突触毒性作用,还可以消除慢性oAβ_(1-42)诱导的海马神经元细胞突触毒性作用。Objective To investigate the effect of Anle138b on chronic synaptic toxicity of hippocampal neurons induced by Aβ1-42 oligomer(oAβ_(1-42)).Methods Primary hippocampal neurons were cultured and divided into control group(without any treatment),oAβ_(1-42)group(treated with 100 nmol/L oAβ_(1-42)for 7 d),Anle138b group(treated with 50 nmol/L Anle138b for 2 d),oAβ_(1-42)+Anle138b group(treated with 100 nmol/L oAβ_(1-42)and 50 nmol/L Anle138b for 7 d),and 2 d oAβ_(1-42)+Anle138b group(treated with 100 nmol/L oAβ_(1-42)for 7 d and 50 nmol/L Anle138b for the last 2 d of oAβ_(1-42)treatment).After treatment,the unicell patch clamp technique was used to record the amplitude,frequency,and half-decay time of spontaneous excitatory postsynaptic currents(sEPSCs).Results There were no significant differences in the amplitude and half-decay time of sEPSCs between the three groups(F=2.215,1.043,P>0.05).There was a significant difference in the frequency of sEPSCs between the three groups(F=15.490,P<0.001),and pairwise comparison showed that compared with the control group,the oAβ_(1-42)group had a significant increase in the frequency of sEPSCs(q=6.507,P<0.001);compared with the oAβ_(1-42)group,the oAβ_(1-42)+Anle138b group and the 2 d oAβ_(1-42)+Anle138b group had a significant reduction in the frequency of sEPSCs(q=9.517,9.471,P<0.001),while there was no significant difference in half-decay time between the other groups(P>0.05).Conclusion Anle138b can not only prevent the chronic synaptic toxicity of hippocampal neurons induced by oAβ_(1-42),but also eliminate the chronic synaptic toxicity induced by oAβ_(1-42).

关 键 词：阿尔茨海默病 β淀粉样蛋白寡聚体 Anle138b 海马 神经元 电生理 

分 类 号：R338.8[医药卫生—人体生理学]