高原低氧致听力下降谷氨酸能突触通路调控研究  

Study on the Egulation of Glutamatergic Synapse Pathway in High-Altitude Hypoxia-Induced Hearing Impairment

作　　者：苗紫林 拉宗[1] 丹增堪孜 赵冰涵 龚嘎蓝孜[1] MIAO Zilin;Lazong;Danzeng-Kanzi;ZHAO Binghan;Gongga-Lanzi(Medical College,Tibet University,Lhasa 850000,China;Pediatric Surgery Department of People's Hospital of Lhasa,Lhasa 850000,China)

机构地区：[1]西藏大学医学院,西藏拉萨850000 [2]西藏拉萨市人民医院小儿外科,西藏拉萨850000

出　　处：《高原科学研究》2023年第4期67-75,共9页Plateau Science Research

基　　金：国家自然科学基金联合重点项目(U22A20340);国家自然科学基金项目(82060588);西藏自治区科技计划项目重点研发计划(XZ202301ZY0011G);西藏大学青年博士学术发展支持项目(zdbs202216)。

摘　　要：目的:探讨谷氨酸能突触通路是否参与高原低氧环境所致的大鼠听力下降过程。方法:将72只雄性Wistar大鼠随机分为移居高原组(15天、30天、60天)和平原对照组,每组各18只大鼠,用听觉脑干电位检测移居高原组和平原对照组听力情况,然后提取第30天听力损伤组与对照组大鼠的耳蜗组织,进行转录组测序,并对其差异基因进行分析。在谷氨酸能突触通路富集的差异基因中筛选目标基因进行RT-qPCR验证。结果:与平原对照组相比,大鼠移居高原15天开始出现听力阈值增高,30天达到峰值,到60天时ABR阈值恢复正常,其阈值与平原对照组无明显差别。听力损伤最显著的移居高原30天组大鼠和平原对照组比较发现共有1329个差异基因,其中上调基因572个,下调基因757个。KEGG通路富集分析显示:谷氨酸能突触通路参与了高原低氧所致听力下降过程(P<0.05),富集到谷氨酸能突触通路的差异基因共有24个,均为低表达基因,其中Slc1a2基因与听力下降相关。GO功能富集分析结果显示:与谷氨酸能突触通路相关的谷氨酸受体活性、离子型谷氨酸受体活性以及细胞外谷氨酸门控离子通道活性被显著富集(P<0.05)。通过对谷氨酸能突触通路中与听力损伤相关的Slc1a2基因进行RT-qPCR验证,发现其结果与转录组测序结果一致。结论:高原低氧环境会导致听力急性损伤,随大鼠移居高原时间延长会出现听力习服。谷氨酸能突触通路参与了高原低氧环境所致的大鼠听力下降过程,其中Slc1a2基因的下调可能与谷氨酸能突触通路参与调控的高原低氧所致听力损伤相关。Objective To investigate whether the glutamatergic synaptic pathway is involved in the hearing impairment Process Induced by high-altitude hypoxic Environment in Rats.Methods Seventy-two male Wistar rats were randomly divided into groups for high-altitude exposure(15 days,30 days,60 days) and a plain control group,with 18 rats in each group.Auditory Brainstem Response(ABR) was used to assess the hearing status of the high-altitude exposure and control groups.Subsequently,cochlear tissues were extracted from rats with hearing impairment and the control group on the 30th day for transcriptome sequencing.Differential gene analysis was performed using the obtained data.Target genes from the differentially expressed genes enriched in the glutamatergic synaptic pathway were selected for RT-qPCR validation.Results Comparing with the plain control group,an elevation in hearing threshold was observed in rats exposed to high altitude starting from 15 days,reaching its peak at 30 days.By the 60th day,the ABR threshold in rats had returned to normal,showing no significant difference from the plain control group.A comparison between rats with significant hearing impairment in the high-altitude group at 30 days and the plain control group revealed 1 329 differentially expressed genes,including 572 upregulated genes and 757 downregulated genes.KEGG pathway enrichment analysis indicated the involvement of the glutamatergic synaptic pathway in the process of high-altitude hypoxia-induced hearing impairment(P<0.05).Among the differentially expressed genes enriched in the glutamatergic synaptic pathway,24 genes were identified,all of which were underexpressed,with the Slc1a2 gene showing a correlation with hearing impairment.GO functional enrichment analysis demonstrated significant enrichment(P<0.05) in glutamate receptor activity,ionotropic glutamate receptor activity,and extracellular glutamate-gated ion channel activity related to the glutamatergic synaptic pathway.RT-qPCR validation of the Slc1a2 gene,associated with hearing i

关 键 词：低氧 听力下降 谷氨酸能突触 Slc1a2 

分 类 号：R764[医药卫生—耳鼻咽喉科]