摘要
目的研究瑞芬太尼对异氟醚引起的新生大鼠海马神经毒性急性期和远期影响及其可能机制。方法将出生7天的大鼠随机分成4组:对照组(Sham组)、异氟醚组(Iso组)、异氟醚+切开组(Iso+I组)及异氟醚+切开+瑞芬太尼组(Ref组),采用每天2 h连续3天的处理方式模拟临床多次麻醉暴露。在第3天麻醉结束后6 h取新鲜海马组织用Western blot检测NF-κB p65蛋白入核的比例,q-RT-PCR检测炎症因子IL-1β、IL-6和TNF-α的mRNA的相对表达量;灌注取脑后用免疫荧光计数离子钙接头蛋白抗原分子-1 (ionized calcium binding adaptor molecule 1,IBA1)阳性细胞数量。大鼠在出生后的第65天进行被动回避实验,观察其学习与记忆能力。结果与Sham组相比,Iso组和Iso+Ⅰ组NF-κB p65蛋白入核的比例显著增加,IL-1β与TNF-α的mRNA的表达量上调,而且这种神经毒性在幼鼠成年后表现为学习与记忆障碍,然而瑞芬太尼显著改善由异氟醚多次暴露所致的神经炎症反应及学习记忆障碍。结论瑞芬太尼改善异氟醚致新生大鼠神经炎症反应,可能通过NF-κB p65通路发挥作用。
ObjectiveTo explore the mechanisms of effect of remifentanil on isoflurane induced newborn rat hippocampal neurotoxicity and observe the effect of remifentanil on isoflurane induced long-term effect. MethodsPostnatal day-7 rats were randomly divided into four groups,the control group (Sham group),isoflurane group (Iso),isoflurane+incision group (Iso+I) and isoflurane+incision+remifentanil group (Ref).We used 2 hours a day for 3 consecutive days to mimic the clinical multiple anesthesia exposure.Western blot was used to detect the proportion of NF-κB p65 protein transferred into the nucleus;q-RT-PCR was used to detect the mRNA expression of inflammatory factors IL-1β,IL-6 and TNF-α;immunofluorescence was used to count ionized calcium binding adaptor molecule 1 (IBA1) positive cells numbers.Meanwhile,on the 65th day,passive avoidance test was used to observe the learning and memory ability. ResultsCompared with the Sham group,in Iso and Iso+I group,isoflurane significantly increased the proportion of NF-κB p65 protein transferred into the nucleus,raised the mRNA expression of TNF-α and IL-1β,and induced learning and memory disorders after the rats matured.However,remifentanil significantly improved repeated isoflurane exposure- induced neruoinflammation and learning and memory disorders. ConclusionsThe mechanism of improvement of remifentanil on isoflurane-induced neurotoxicity in newborn rats may be through the NF-κB p65 pathway.
作者
郭莹
潘波
黄绍强
GUO Ying;PAN Bo;HUANG Shao-qiang(Department of Anesthesiology,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200090,China)
出处
《复旦学报(医学版)》
CAS
CSCD
北大核心
2019年第1期8-13,共6页
Fudan University Journal of Medical Sciences
基金
上海市自然科学基金(15ZR1404600)~~
关键词
发育大脑
瑞芬太尼
异氟醚
神经炎症
developing brain
remifentanil
isoflurane
neuroinflammation