摘要
目的探讨右美托咪定(dexmedetomidine,DEX)在七氟醚(sevoflurane,SEVO)诱导新生大鼠海马神经元损伤中的作用机制。方法采用暴露于2.5%七氟醚6 h的40只雄性SD幼鼠(无特定病原体等级,7 d龄,体质量10~15 g)为动物模型,并在暴露前将DEX按5μg·kg^(-1)的剂量或等量的生理盐水腹膜内注射SEVO暴露组和对照组幼鼠体内。分离大鼠海马组织,采用流式细胞术分析细胞凋亡,免疫荧光染色分析内质网(endoplasmic reticulum,ER)应激标记物(PERK、Caspase-12)的表达,Western blot分析MAPK(ERK、JNK和P38)信号通路表达。结果联合给予SEVO和DEX大鼠的海马细胞凋亡程度比单独暴露SEVO的大鼠降低[(24.27±4.52)vs(43.90±10.94),P<0.05],并且PERK及Caspase-12表达的升高程度低于仅用SEVO处理的大鼠(P<0.05)。与对照组相比,单独暴露于SEVO大鼠的p-ERK、p-JNK和p-P38表达均增加(P<0.05)。联合给予SEVO和DEX大鼠的p-ERK、p-JNK和p-P38表达低于仅用SEVO处理的大鼠(P<0.05)。结论右美托咪定可能通过抑制MAPK信号通路减轻ER应激,改善七氟醚引起的神经毒性。
Objective To investigate the mechanism of dexmedetomidine(DEX)in sevoflurane(SEVO)induced hippocampal neuron injury in neonatal rats.Methods Forty male Sprague-Dawley(SD)rats(7-day-old,10~15 g)were given i.p.injections of saline or DEX(μg·kg^(-1)),and then exposed for 6 h to 2.5%SEVO.After rat hippocampal tissue was collected and separated,flow cytometry,immunofluorescence staining and Western blotting were used respectively to detect cell apoptosis,expression of endoplasmic reticulum(ER)stress markers PERK and Caspase-12,and expression of MAPK signal pathway-related proteins(ERK,JNK and P38).Results The apoptotic rate of hippocampal cells was significantly lower(24.27±4.52 vs 43.90±10.94,P<0.05),and the expression of PERK and Caspase-12 was also obviously decreased in the rats after co-administration of SEVO and DEX than those exposed to SEVO alone(P<0.05).The expression levels of p-ERK,p-JNK and p-P38 were significantly increased in the rats after SEVO exposure than the control rats(P<0.05),and the levels were lowest in the rats after co-administration(P<0.05).Conclusion DEX alleviates ER stress probably by inhibiting the MAPK signaling pathway,and then improves neurotoxicity induced by SEVO.
作者
白鹏祖
张利亮
张海盛
姚泽宇
BAI Pengzu;ZHANG Liliang;ZHANG Haisheng;YAO Zeyu(Department of Anesthesiology,Qinghai Red Cross Hospital,Xining,Qinghai Province,810000,China)
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2021年第10期964-969,共6页
Journal of Third Military Medical University
基金
青海省自然科学基金项目(2019-ZJ-7085)。
关键词
右美托咪定
MAPK通路
七氟醚
大鼠
海马
内质网应激
dexmedetomidine
MAPK pathway
sevoflurane
rats
hippocampus
endoplasmic reticulum stress