右美托咪定干扰七氟烷致老年糖尿病大鼠海马损伤的作用研究  

Dexmedetomidine interferes with sevoflurane-induced hippocampal damage in elderly diabetic rats

作　　者：于冠楠 马伟 白净 郝旭丽 刘铁军 程爱斌 王建军 YU Guannan;MA Wei;BAI Jing(Department of Anesthesiology,North China University of Science and Technology Affiliated Hospital,Hebei,Tangshan 063000,China)

机构地区：[1]华北理工大学附属医院麻醉科,河北省唐山市063000 [2]华北理工大学附属医院重症医学科,河北省唐山市063000

出　　处：《河北医药》2024年第24期3754-3757,共4页Hebei Medical Journal

基　　金：河北省医学科学研究重点课题计划(编号:20191128)。

摘　　要：目的探讨七氟烷致内毒素血症老年糖尿病大鼠海马损伤的可能机制,以及右美咪托啶对海马组织的保护作用。方法24只20周龄的SPF级SD大鼠,分为4组,每组6只,分别为空白对照组(C组)、模型对照组(M组)、七氟烷组(S组)、右美托咪定复合七氟烷组(S+D组)。M、S、M+S组制备老年糖尿病内毒素血症大鼠模型,S组实行七氟烷吸入麻醉,M+S组经右美咪托啶预处理后再实行七氟烷麻醉。模型制备成功后观察大鼠认知功能和神经行为学的变化;HE染色观察大鼠海马组织的损伤情况;Western blot法检测内质网应激相关蛋白的表达情况。结果七氟烷麻醉后大鼠学习记忆能力降低,热敏感性、空间认知能力以及探究行为都有所抑制,而右美咪托啶预处理组大鼠的神经行为指标均有所改善(P<0.05);七氟烷麻醉后大鼠海马组织凋亡蛋白casepase-12增加,内质网应激相关蛋白GRP78增加,同时ATF6、CHOP蛋白表达升高;右美咪托啶预处理组大鼠相关蛋白表达均较单纯麻醉组有所降低(P<0.05)。结论七氟烷吸入麻醉可导致内毒素血症老年糖尿病大鼠认知功能障碍,海马组织病理损伤,而右美咪托啶可缓解七氟烷所致的认知障碍和海马损伤,并可能通过内质网应激-ATF6-CHOP-凋亡通路发挥作用。Objective To investigate the possible mechanism of cognitive dysfunction in sevoflurane-induced elderly diabetic rats with endotoxemia and the protective effect of dexmedetomidine on hippocampal tissue.Methods A total of 24 Sprague-Dawley(SD)rats with 20 weeks old and specific pathogen-free(SPF)level were divided into 4 groups,with 6 rats in each group,including blank control group(Group C),model control group(Group M),sevoflurane group(Group S),and dexmedetomidine combined sevoflurane group(Group S+D).Rats in Group C were not treated.Rats in other groups were subjected to the modeling of senile diabetic endotoxemia.Rats in Group S were anaesthetized with sevoflurane for inhalation,and those in Group M+S were injected with dexmedetomidine and then anaesthetized with sevoflurane.After successful modeling,cognitive function and neurobehavioral changes were observed.Hippocampal damage was detected by H&E staining.The expressions of endoplasmic reticulum stress(ERS)proteins were detected by Western blot.Results After sevoflurane anesthesia,the learning and memory ability,thermal sensitivity,spatial cognitive ability and exploration behavior were significantly impaired in Group S than those of Group M.However,the neurobehavioral indexes were improved in Group S+D(P<0.05).The apoptotic protein Casepase-12 and ERS-related proteins glucose-regulated protein 78(GRP78),activating transcription factor 6(ATF6)and C/EBP Homologous Protein(CHOP)were significantly upregulated in Group S compared with those of Group M.They were significantly downregulated in Group S+D than those of Group S(P<0.05).Conclusion Sevoflurane inhalation anesthesia can induce cognitive dysfunction and hippocampus injury in elder endotoxemia diabetic rats,which can be relieved by dexmedetomidine via mediating the ERS-ATF6-CHOP apoptosis pathway.

关 键 词：右美咪托啶 七氟烷 麻醉 认知功能障碍 内质网应激 

分 类 号：R587.1[医药卫生—内分泌]