右美托咪定通过减少脑源性神经营养因子表达抑制MAPK/ERK信号通路活化减轻大鼠分娩疼痛  

Dexmedetomidine alleviates the labor pain by inhibiting the activation of MAPK/ERK signaling pathway due to reduced BDNF expression in rats

作　　者：葛亮 张鹏 杜丽芳[1] 韩旭东[1] Ge Liang;Zhang Peng;Du Lifang;Han Xudong(Gansu Maternal and Child Health Hospital,Department of Anesthesiology,Gansu Central Hospital,Lanzhou 730050,China)

机构地区：[1]甘肃省妇幼保健院,甘肃省中心医院麻醉科,兰州730050

出　　处：《解剖学杂志》2024年第1期29-34,共6页Chinese Journal of Anatomy

基　　金：甘肃省自然科学基金(20JR10RA423)。

摘　　要：目的:从脑源性神经营养因子(BDNF)/丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)信号通路探讨不同剂量右美托咪定(Dex)对大鼠分娩疼痛疗效的影响及其机制。方法:建立大鼠妊娠模型;将实验动物随机分为4组,对照组,大鼠自然分娩,未行任何处理;Dex组,大鼠产程启动至产下最后1个仔鼠期间,分别静脉注射50、100μg/kg和200μg/kg右美托咪定;免疫组织化学显色检测大鼠大脑皮质顶叶与子宫内膜组织中BDNF的表达;热水甩尾法测定大鼠分娩时的痛阈值及Richmond躁动镇静评分;qRT-PCR与免疫印迹检测大脑皮质顶叶与子宫内膜组织迅速加速纤维肉瘤蛋白(Raf)、ERK、cAMP反应元件结合蛋白(CREB)及强啡肽(DYN)的表达。结果:注射Dex后,大鼠大脑皮质顶叶与子宫内膜中BDNF蛋白表达水平显著降低,且Dex剂量显著影响BDNF蛋白表达水平。随着Dex剂量增加,大鼠分娩时的痛阈值明显提高,Richmond躁动镇静评分降低。与对照组相比,注射Dex后,大脑皮质顶叶与子宫内膜中Raf、ERK、CREB mRNA与蛋白表达水平显著下降,DYN mRNA与蛋白表达水平显著升高。相关性分析显示,大脑皮质顶叶BDNF表达与Raf、ERK、CREB表达呈正相关,而与DYN表达呈负相关;子宫内膜BDNF表达与Raf、ERK表达无相关性,与CREB表达呈正相关,与DYN表达呈负相关。结论:静脉注射Dex对大鼠分娩疼痛抑制作用明显,可能与通过BDNF激活MAPK/ERK信号通路密切相关。Objective:To investigate the effect and mechanism of different doses of dexmedetomidine(Dex)on labor pain in rats through the brain-derived neurotrophic factor(BDNF)/mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods:A rat pregnancy model was established.The experimental animals were randomly divided into four groups.The rats in the control group underwent natural childbirth without any treatment;the three Dex groups,where rats were intravenously injected with 50,100,and 200μg/kg Dex during the initiation of labor until the birth of the last pup.Immunohistochemistry was used to detect the BDNF expression in rat cortical parietal lobe of the brain and endometrial tissue.The tail immersion assay was used to determine the pain threshold and Richmond agitation-sedation scale scores during rat labor.The expression levels of rapidly accelerated fibrosarcoma(Raf),ERK,cAMP response element binding protein(CREB)and dynorphin(DYN)were detected by qRT-PCR and Western blotting in rat cortical parietal lobe of the brain and endometrial tissue.Results:The expression level of BDNF protein in rat cortical parietal lobe of the brain and endometrial tissue was significantly decreased by Dex in a dose-dependent manner.With the increase of Dex dose,intravenous injection of Dex significantly increased the pain threshold of laboring rats and decreased the Richmond agitation and sedation scores.Compared with the control group,the mRNA and protein expression levels of Raf,ERK and CREB in rat cortical parietal lobe of the brain and endometrium were significantly decreased after injection of Dex,while the mRNA and protein expression levels of DYN were significantly increased.Correlation analysis showed that BDNF expression was positively correlated with Raf,ERK and CREB expression in the cortical parietal lobe of the brain,but negatively correlated with the expression of DYN.BDNF expression had no correlation with Raf and ERK expression in endometrium,but was positively correlated w

关 键 词：右美托咪定 脑源性神经营养因子 分娩 疼痛 丝裂原活化蛋白激酶 细胞外信号调节激酶 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学] R34[医药卫生—基础医学]