目的 基于MAPK/ERK信号通路探讨不同剂量右美托咪定对硬膜外分娩镇痛的影响。方法 将符合纳入标准的200例分娩产妇随机分为：非硬膜外镇痛组（C组）、硬膜外镇痛联合生理盐水组（N组）、硬膜外镇痛联合静脉泵注右美托咪定0.5 μg/kg组（D1组）、硬膜外镇痛联合静脉泵注右美托咪定0.75μg/kg组（D2组）和硬膜外镇痛联合静脉泵注右美托咪定1 μg/kg组（D3组）,每组40例。参照Ramsay镇静评分量表及VAS评分法记录各组的镇静剂疼痛评分,检测产后2 h阴道出血量,Apgar评分法对胎儿出生后1、5、10 min进行常规评分,检测第一、第二产程的持续时间,监测产妇平均动脉压（MAP）、心率（HR）,记录不良反应（ARs）。RT-PCR检测胎盘中Raf、ERK、CREB及DYN的mRNA及蛋白的表达。建立大鼠妊娠模型,将造模成功的孕鼠随机分为4组,即空白对照组C组,右美托咪定50 μg/kg（D1组）,右美托咪定100 μg/kg（D2组）,右美托咪定200 μg/kg（D3组）。大鼠分娩时的痛阈值测定用热水甩尾法,采用Richmond躁动镇静评分量表进行评分;RT-PCR和WB检测大脑灰质顶叶区、脊髓腰膨大段、子宫肌层组织Raf、ERK、CREB及DYN的mRNA及蛋白含量变化。结果 结果发现各组分娩孕妇的年龄、BMI、孕周、宫颈扩张、产后 2 h 内阴道出血量、镇痛前Ramsay评分、镇痛前VAS评分和新生儿Apgar评分间无统计学意义。D1、D2、D3组在T1―T3的Ramsay评分大于N组,第一产程、第二产程、MAP、HR、VAS评分小于N组,Raf、ERK和CREB mRNA明显低于N组及C组,mRNA明显高于N组及C组,差异有统计学意义。在大鼠妊娠模型中,与C组比较,给药100 μg/kg和200 μg/kg右美托咪定增加甩尾潜伏期,Richmond 躁动镇静评分低于C组,右美托咪定组降低了大鼠大脑灰质顶叶区、脊髓腰膨大段、子宫肌层组织MAPK/ERK信号通路的mRNA及蛋白含量变化,差异有统计学意义。结论 右美托咪定用于硬膜外分娩镇痛,通过降低了MAPK/ERK信号通路的表达,可有效缓解分娩疼痛。
Abstract
Objective To investigate the effect of different doses of dexmedetomidine on epidural labor analgesia for mothers and infants based on MAPK/ERK signaling pathway. Methods 200 puerperae who met the inclusion criteria were randomly divided into: non-epidural analgesia group (group C), epidural analgesia combined with normal saline group (group N), epidural analgesia combined with intravenous injection of dexamethasone Detomidine 0.5μg/kg group (group D1), epidural analgesia combined with intravenous injection of dexmedetomidine 0.75μg/kg group (D2 group) and epidural analgesia combined with intravenous injection of dexmedetomidine 1μg/kg group (D3 group), 40 cases in each group. The Ramsay sedation scale and VAS score were used to record the pain scores of sedatives in each group. The volume method was used to detect the amount of vaginal bleeding at 2 h postpartum. RT-PCR was used to detect the mRNA and protein expressions of Raf, ERK, CREB and DYN in the placenta. A rat pregnancy model was established, and the successfully modeled pregnant rats were randomly divided into 4 groups, namely blank control group C, dexmedetomidine 50 μg/kg (group D1), dexmedetomidine 100 μg/kg (group D2) ), dexmedetomidine 200 μg/kg (group D3). The pain threshold of rats during childbirth was determined by hot water tail flick method, and the Richmond agitation and sedation scale was used for scoring; RT-PCR and WB were used to detect the parietal lobe region of gray matter, spinal cord lumbar enlargement, and myometrium tissue Raf, ERK, Changes in mRNA and protein content of CREB and DYN. Results TResults There were no significant differences in age, BMI, gestational week, cervical dilation, postpartum vaginal bleeding volume, pre-analgesic Ramsay score, pre-analgesic VAS score and neonatal Apgar score among all groups. The Ramsay score in T1-T3 in D1-D3 group was higher than that in N group, the VAS score was lower than that in N group, the mRNA of Raf, ERK and CREB in D1-D3 group was significantly lower than that in N and C group, and the mRNA was significantly higher than that in N and C group, with statistical significance. In the rat pregnancy model, compared with group C, administration of 100μg/kg and 200 μg/kg dexmedetomidine increased tail flick latency, Richmond agitation sedation score was lower than group C. Dexmedetomidine group decreased the mRNA and protein contents of MAPK/ERK signaling pathway in the parietal region of brain gray matter, lumbar enlargement of spinal cord and myometrium of rats, and the differences were statistically significant. Conclusion Dexmedetomidine is used for epidural labor analgesia. By reducing the expression of MAPK/ERK signaling pathway, it can effectively relieve labor pain without obvious maternal.
关键词
MAPK/ERK /
右美托咪定 /
硬膜外分娩镇痛
Key words
MAPK/ERK /
dexmedetomidine /
epidural labor pain relief
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基金
甘肃省科技计划项目“从mapk/ERK信号通路探讨不同剂量右美托咪定对硬膜外分娩镇痛母婴结局的影响及机制”（20JR1ORA423）
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