前列腺素E2对雌性小鼠下丘脑视前区正中核热敏神经元放电活动的影响及其机制  

Effect of prostaglandin E2 on discharge activity of warm-sensitive neurons in median preoptic nucleus of hypothalamus in female mice and its mechanism

作　　者：侯晓钰[1] 李娅[1] 宋宜安 何田慧 张洁[2] 胥建辉[2] HOU Xiaoyu;LI Ya;SONG Yian;HE Tianhui;ZHANG Jie;XU Jianhui(Department of Obstetrics,First Affiliated Hospital,Chengdu Medical College,Chengdu 610500,China;Key Laboratory of Thermoregulation and Inflammation of Sichuan Universities,Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都医学院第一附属医院产科,四川成都610500 [2]成都医学院体温与炎症四川省高校重点实验室,四川成都610500

出　　处：《吉林大学学报(医学版)》2025年第1期17-25,共9页Journal of Jilin University:Medicine Edition

基　　金：国家自然科学基金项目(32100926);四川省成都市卫健委医学科研项目(2022093);四川省医学会科研项目(Q22010);成都医学院科研项目(CYZYB21-16)。

摘　　要：目的:探讨致热介质前列腺素E_(2)(PGE_(2))对雌性小鼠下丘脑视前区正中核(MnPO)热敏神经元(WSNs)放电活动的影响,并阐明其作用机制。方法:制作雌性小鼠MnPO冠状脑片,灌流含有突触阻断剂(STBs)的人工脑脊液(ACSF),改变灌流液温度的同时应用膜片钳技术检测神经元的放电频率,鉴定WSNs。32个MnPO WSNs分为基础放电组(n=32)和PGE_(2)组(n=32),采用膜片钳技术检测MnPO WSNs分别灌流ACSF和1μmol·L-1PGE_(2)后的放电频率。选择灌流PGE_(2)后放电频率明显改变且活性良好的MnPO WSNs(n=21),分为PGE_(2)受体E系列前列腺素受体(EP)1拮抗剂(EP1 ant)+PGE_(2)组(n=7)、EP3 ant+PGE_(2)组(n=7)和EP4 ant+PGE_(2)组(n=7),采用膜片钳技术检测MnPO WSNs分别灌流3μmol·L-1EP1 ant和1μmol·L-1PGE_(2)混合液、10μmol·L-1EP3 ant和1μmol·L-1PGE_(2)混合液及10μmol·L-1EP4 ant和1μmol·L-1PGE_(2)混合液后的放电频率。结果:灌流含有STBs的ACSF后,共有188个雌性小鼠的MnPO神经元进行了内在温度敏感系数(以m值表示)的鉴定,其中32个神经元的m值≥0.8,被鉴定为MnPO WSNs,占所有记录神经元的17%。与基础放电频率比较,加入PGE_(2)后MnPO的放电频率明显降低(P<0.05);与PGE_(2)组比较,EP3 ant+PGE_(2)组MnPO WSNs的放电频率百分比改变降低(P<0.05);与PGE_(2)组比较,EP1 ant+PGE_(2)组MnPO WSNs的放电频率的百分比改变差异无统计学意义(P>0.05);与PGE_(2)组比较,EP4 ant+PGE_(2)组MnPO WSNs的放电频率的百分比改变差异无统计学意义(P>0.05)。结论:雌性小鼠MnPO存在约17%的WSNs;PGE_(2)可通过突触后的机制经EP3受体直接抑制雌性小鼠MnPO WSNs的放电活动。Objective:To discuss the effect of prostaglandin E_(2)(PGE_(2)),a pyrogenic mediator,on the discharge activity of warm-sensitive neurons(WSNs)in median preoptic nucleus(MnPO)of hypothalamus in the female mice,and to clarify its mechanism.Methods:Coronal brain slices of MnPO were prepared from the female mice.The slices were then perfused with artificial cerebrospinal fluid(ACSF)containing synaptic transmission blockers(STBs).The discharge frequency was monitored using the patch clamp technique while changing the temperature of the perfusate to identify the WSNs.A total of 32 MnPO WSNs were divided into base line group(n=32)and PEG2(n=32).The patch clamp technique was employed to monitor the discharge frequencies of MnPO WSNs following the perfusion of ACSF and 1μmol·L-1 PGE_(2),respectively.The MnPO WSNs with good activity and significant change in discharge frequency after PGE_(2)perfusion were divided into PGE_(2)receptor E-series prostaglandin receptrol(EP)1 antagonist(EP1 ant)+PGE_(2)group(n=7),EP3 ant+PGE_(2)group(n=7),and EP4 ant+PGE_(2)group(n=7).The patch clamp technique was used to monitor the discharge frequencies of MnPO WSNs following the perfusion of 3μmol·L-1 EP1 ant and 1μmol·L-1 PGE_(2)mixture,10μmo·l L-1 EP3 ant and 1μmo·l L-1 PGE_(2)mixture,and 10μmo·l L-1 EP4 ant and 1μmo·l L-1 PGE_(2)mixture,respectively.Resluts:After perfuson of the ACSF containing STBs,a total of 188 MnPO neurons from the female mice with an intrinsic temperature sensitivity coefficient(m value)were identified;out of these,32 neurons had an m value of≥0.8 and were identified as MnPO WSNs,accounting for approximately 17%of all recorded neurons.Compared with baseline discharge frequency,the discharge frequency of MnPO WSNs after addition of PGE_(2)was decreased(P<0.05).Compared with PGE_(2)group,the percentage change in discharge frequency of MnPO WSNs in EP3 ant+PGE_(2)group was significantly decreased(P<0.05).Compared with PGE_(2)group,the percentage change in discharge frequency of MnPO WSNs in EP1 ant+PGE_(

关 键 词：发热 前列腺素E2 视前区正中核 热敏神经元 EP3受体 

分 类 号：R714[医药卫生—妇产科学] R339.6[医药卫生—临床医学]