伏隔核ERK信号转导通路在右美托咪定抑制丙泊酚复吸中的作用研究  

Effect of ERK signal transduction pathway in nucleus accumbens on inhibition of propofol relapse by dexmedetomidine

作　　者：王本福 陈君[1,2] 董张雷 王思聪[3] 岑柏言 沈杨昊 苏颖 WANG Benfu;CHEN Jun;DONG Zhanglei;WANG Sicong;CEN Boyan;SHEN Yanghao;SU Ying(The Eye Hospital of Wenzhou Medical University,Wenzhou 325000 Zhejiang,China)

机构地区：[1]温州医科大学附属眼视光医院,浙江省温州325000 [2]温州医科大学眼视光学院(生物工程学院),浙江省温州325000 [3]温州医科大学附属第二医院、育英儿童医院 [4]温州医科大学第二临床医学院

出　　处：《现代实用医学》2025年第3期233-237,共5页Modern Practical Medicine

基　　金：国家自然科学基金(81771431);温州市科技计划项目(Y20210126);浙江省医药卫生科技计划项目(2021437659)。

摘　　要：目的探讨伏隔核(NAc)细胞外信号调节激酶(ERK)信号转导通路在右美托咪定(DEX)抑制丙泊酚戒断大鼠复吸行为中的作用。方法雄性SD大鼠按固定比率1强化程序建立丙泊酚静脉自身给药行为。戒断14 d后,选取24只随机分成3组(=8),溶剂对照组(对照组)、DEX 10μg/kg组(10 g/kg组)和DEX 20μg/kg组(20μg/kg组),观察腹腔注射DEX对丙泊酚大鼠复吸行为的影响。Western blot检测上述各组大鼠NAc内磷酸化ERK的表达水平。另有18只na ve SD大鼠随机分分成3组(n=6),对照组、10μg/kg组和20μg/kg组,以观测DEX对大鼠活动度的影响。结果大鼠的有效鼻触次数随着丙泊酚自身给药训练天数的增加趋于稳定,而无效鼻触逐渐降低趋向于零(<0.05),成功建立丙泊酚静脉自身给药大鼠模型。复吸行为检测发现,与对照组相比,10 g/kg组和20 g/kg组大鼠的有效鼻触明显降低,即腹腔注射DEX明显抑制了大鼠有效鼻触(<0.05),DEX 20μg/kg显著抑制NAc ERK磷酸化水平(<0.05),且抑制了大鼠的活动度(P<0.05),而DEX 10μg/kg对大鼠的活动度没有明显影响(>0.05)。结论DEX可能通过抑制NAc ERK信号转导通路减弱丙泊酚的复吸行为。Objective To investigate the effect of extracellular signal-regulated kinase(ERK)signaling pathway in the nucleus accumbens(NAc)on inhibition of propofol relapse by dexmedetomidine(DEX).Methods Intravenous self-administration of propofol was established in male SD rats according to a fixed ratio 1 reinforcement program.After a fourteen-day withdrawal period,the rats were randomly divided into control group,DEX 10μg/kg group,and DEX 20μg/kg group,with eight rats in each group.Evaluate the impact of DEX intraperitoneal injected on the reinstatement of propofol-seeking behavior.The expression of phosphorylated ERK in NAc was detected by western blot.Eighteen naive rats were divided into control group,DEX 10μg/kg group,and DEX 20μg/kg group at the same time(six rats per group),and observe their motor activity.Results The number of effective nasal contact in rats gradually increased and tended to be stable with the training days of self-administration of propofol,while the number of ineffective nasal contact gradually decreased and tended to zero(P<0.05),which confirmed the establishment of a reliable propofol intravenous self-administration model.The results of the relapse behavior detection test showed that the effective nasal contact of the rats in the DEX 10μg/kg group,and DEX 20μg/kg group were decreased than that of control group(P<0.05).The western blot assay showed that the phosphorylated expression of ERK in DEX 20μg/kg group was lower than that of control group(P<0.05),and significantly decreased the mobilities of the rats(P<0.05),while DEX 10μg/kg group could’t alter the mobilities obviously(P>0.05).Conclusions DEX may reduce the relapse of propofol by inhibiting the NAcERK signal transduction pathway.

关 键 词：丙泊酚 伏隔核 细胞外信号调节激酶信号转导通路 右美托咪定 

分 类 号：R614[医药卫生—麻醉学]