CAJ | 학술논문

目的：探究KA1亚受体的表达上调在内质网应激致海马神经元死亡中的作用。方法将70只成年雄性昆明小鼠随机分为红藻氨酸组（KA组）、衣霉素组（TM）500μg/ml组、TM1000μg/ml组和TM2000μg/ml组，海马内注射KA或不同浓度TM，不同时间段（1、2、3、4、5、8、12 h）灌注取脑，灌注取脑前进行Bederson体征评分，全脑切片FJB染色和免疫组化分析。结果 KA组第3、4、5、8h和TM2000μg/ml组第4、5小时，Bederson体征评分表明中枢神经功能出现明显损伤，FJB染色示海马内细胞死亡增加，免疫组化示KA1和P-eIF2α在海马神经元的表达明显上调（P<0.05）。结论海马内注射KA或TM后结果显示内质网应激中有KA1的表达，在神经元凋亡过程中膜外受体KA1可能首先接受凋亡信号，并向细胞内传导，引起内质网功能紊乱，诱发内质网应激，并进一步促使神经元调亡。
목적：탐구KA1아수체적표체상조재내질망응격치해마신경원사망중적작용。방법장70지성년웅성곤명소서수궤분위홍조안산조（KA조）、의매소조（TM）500μg/ml조、TM1000μg/ml조화TM2000μg/ml조，해마내주사KA혹불동농도TM，불동시간단（1、2、3、4、5、8、12 h）관주취뇌，관주취뇌전진행Bederson체정평분，전뇌절편FJB염색화면역조화분석。결과 KA조제3、4、5、8h화TM2000μg/ml조제4、5소시，Bederson체정평분표명중추신경공능출현명현손상，FJB염색시해마내세포사망증가，면역조화시KA1화P-eIF2α재해마신경원적표체명현상조（P<0.05）。결론해마내주사KA혹TM후결과현시내질망응격중유KA1적표체，재신경원조망과정중막외수체KA1가능수선접수조망신호，병향세포내전도，인기내질망공능문란，유발내질망응격，병진일보촉사신경원조망。
Objective To explore the effect of up-regulation of KA1 subunit of the kainate receptor on endoplasmic reticulum stress (ERS)-induced excitotoxic neurodegeneration in mouse hippocampus. Methods Seventy adult male KM mice were subjected to microinjections into the hippocampus of kainic acid (KA) or 500, 1000, or 2000μg/ml tunicamycin (TM). At 1, 2, 3, 4, 5, 8, and 12 h after the injections, the mice were assessed for Bederson scores and sacrificed for FJB staining and immunofluorescence observation of the brain slices. Results At 3, 4, 5, and 8 h after KA injection and at 4 and 5 h after of 2000μg/ml TM injection, the mice showed severe central nervous system dysfunction, and FJB staining revealed increased cell death in the hippocampus, where up-regulated expressions of KA1 receptor and ERS marker P-eIF2α were found by immunofluorescence staining (P<0.05). Conclusion Microinjection of KA or TM into the hippocampus causes neuronal death and ERS with up-regulated expression of KA1. In this process of neuronal apoptosis, the membrane receptor KA1 receives the apoptosis signal and transfers it to the inside of the cells to cause cell endoplasmic reticulum dysfunction and ERS response, which ultimately leads to neuronal death.