右美托咪定对异氟醚致幼龄大鼠海马损伤的保护作用及其机制  

Protective Effect and Mechanism of Dexmedetomidine on Isoflurane-Induced Hippocampal Injury in Young Rats

作　　者：陈永平 武珣 徐采琳 于权麟 孙子涵 王思爽 叶镇邦 陈世增 胡学远 刘焕奇[1] CHEN Yongping;WU Xun;XU Cailin;YU Quanlin;SUN Zihan;WANG Sishuang;YE Zhenbang;CHEN Shizeng;HU Xueyuan;LIU Huanqi(College of Veterinary Medicine,Qingdao Agricultural University,Qingdao 266109,China)

机构地区：[1]青岛农业大学动物医学院,山东青岛266109

出　　处：《中国兽医杂志》2024年第11期11-18,共8页Chinese Journal of Veterinary Medicine

基　　金：国家自然科学基金项目(31902337);山东省现代农业产业技术体系牛产业创新团队资助项目(SDAIT-09-03);山东省自然科学基金青年基金项目(ZR2022QC157)。

摘　　要：为了探明右美托咪定(DEX)对异氟醚致幼龄大鼠海马损伤的保护作用及其机制,本试验选取60只SD幼龄大鼠随机均分为对照组、模型组、DEX干预组和DEX组。对照组未作处理,DEX干预组和DEX组大鼠分别腹腔注射25μg/(kg·bw)DEX;30 min后,模型组和DEX干预组大鼠持续灌注1.5%异氟醚,6 h后处死所有大鼠,分离海马组织,通过苏木素-伊红(H.E.)染色观察海马组织病理学变化,透射电子显微镜观察海马细胞超微结构,酶联免疫吸附测定(ELISA)试剂盒检测海马组织中胱天蛋白酶3(Caspase-3)活性,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测细胞凋亡率,Western blot检测转化生长因子-β(TGF-β)蛋白表达,实时荧光定量PCR(qPCR)检测微小RNA 137(miR-137)表达。结果显示,与对照组相比,模型组大鼠海马神经元排列紊乱、细胞间隙增大,线粒体严重扭曲肿胀、嵴溶解消失,线粒体损伤评分极显著升高(P<0.01),Caspase-3活性显著升高(P<0.05),细胞凋亡率和TGF-β蛋白表达量均极显著升高(P<0.01),miR-137表达水平显著降低(P<0.05);与模型组相比,DEX干预组大鼠海马神经元排列较整齐,仅见少量线粒体肿胀、嵴溶解消失,线粒体损伤评分极显著降低(P<0.01),Caspase-3活性显著降低(P<0.05),细胞凋亡率和TGF-β蛋白表达量极显著降低(P<0.01),miR-137表达水平显著升高(P<0.05);DEX组与对照组相比,所有指标均差异不显著(P>0.05)。结果表明,DEX可改善异氟醚诱导的幼龄大鼠海马损伤,可能与其调控miR-137,抑制TGF-β表达,遏制细胞凋亡的发生有关。This study aimed to investigate the protective effect and mechanism of dexmedetomidine(DEX)on isoflurane-induced hippocampal injury in young rats.Sixty Sprague-Dawley(SD)young rats were randomly divided into four groups:Control group,Model group,DEX intervention group,and DEX group.The Control group received no treatment,while the DEX intervention group and DEX group were intraperitoneally injected with DEX at a dose of 25μg/(kg·bw).After 30 minutes,the Model group and DEX intervention group were continuously infused with 1.5%isoflurane.All rats were sacrificed 6 hours later,and hippocampal tissue was collected for analysis.Hippocampal histopathological change was observed by hematoxylin and eosin(H.E.)staining,hippocampal cell ultrastructure was examined by transmission electron microscopy,cysteine-requiring aspartate protease 3(Caspase-3)activity was measured using an enzyme-linked immuno sorbent assay(ELISA)kit,apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL),transforming growth factor-β(TGF-β)protein expression was analyzed by Western blot,and miR-137 expression was assessed using real-time quantitative PCR(qPCR).The results showed that,compared with the Control group,the Model group exhibited disorganized hippocampal neurons,enlarged intercellular spaces,severely distorted and swollen mitochondria,and dissolution of mitochondrial cristae,the mitochondrial damage score was significantly increased(P<0.01),Caspase-3 activity was elevated(P<0.05),apoptosis rate and TGF-βprotein expression were markedly increased(P<0.01),and miR-137 expression was reduced(P<0.05).In contrast,compared with the Model group,the DEX intervention group showed more orderly neuronal arrangement,only mild mitochondrial swelling,reduced mitochondrial damage score(P<0.01),decreased Caspase-3 activity(P<0.05),significantly lower apoptosis rate and TGF-βprotein expression(P<0.01),and increased miR-137 expression(P<0.05).No significant differences were found between the

关 键 词：右美托咪定 异氟醚 幼龄大鼠 海马损伤 细胞凋亡 miR-137/TGF-β信号通路 

分 类 号：S854.4[农业科学—临床兽医学]