摘要
目的探讨神经病理性痛大鼠母爱行为对子鼠情绪及杏仁核DNA甲基化的影响。方法健康成年sD大鼠48只，体重200～250g，雌雄各半。雌雄大鼠各随机取12只，采用坐骨神经慢性压迫性损伤法制备神经病理性痛模型。于模型制备后10d，大鼠进行交叉配对。取神经病理性痛母鼠的F1代子鼠48只，采用随机数字表法分为2组（n=24）：NP1组、NP2组；取正常母鼠的F1代子鼠48只，采用随机数字表法分为2组（n=24）：S1组和S2组。NP2组和S2组在出生后即互换母鼠喂养，NP1组和S1组由原母鼠喂养。所有子鼠由选定的母鼠喂养至出生后21d，单独饲养30d时进行行为学实验。检测母鼠分娩后回收与舔仔行为，评价其母爱行为；测定子鼠机械痛阈和热痛阈，行高架十字迷宫实验和旷场实验测定子鼠焦虑和抑郁情绪。行为学测试完成后1d，采用Western blot法检测子鼠杏仁核DNA甲基转移酶1（DNMT1）和DNA甲基转移酶3a／b（DNMT3a／b）的表达。结果与S1组或S2组比较，NP1组或NP2组母鼠舔仔潜伏期、回收潜伏期和回收总时间延长，舔仔总时间缩短（P〈0．05或0．01）。4组子鼠机械痛阈和热痛阈比较差异无统计学意义（P〉0．05）。与S1组比较，S2组和NP1组子鼠开放臂与闭合臂停留时间比值和中央格停留时间与周围格停留时间比值降低，杏仁核DNMT1表达上调，总体DNA甲基化水平升高（P〈0．05）；与NP2组比较，S2组与NP1组子鼠开放臂与闭合臂停留时间比值和中央格停留时间与周围格停留时间比值降低，杏仁核DNMT1表达上调，总体DNA甲基化水平升高（P〈0．05）。结论神经病理性痛大鼠母爱行为下降可导致子鼠焦虑、抑郁负面情绪，其机制与子鼠杏仁核DNA甲基化水平增加有关。
Objective To investigate the effects of maternal behaviors in the rats with neuropathic pain （NP） on emotions of offspring rats and the relationship with DNA methylation in the amygdala. Meth- ods Forty-eight healthy adult Sprague-Dawley rats （24 males and 24 females） , weighing 200-250 g, were used in the study. Twelve female and 12 male rats were randomly selected, and NP was induced by chronic constriction injury （ CCI）. Each female rat was mated with one male rat at 10 days after CCI. Fortyeight F1 generation rats of maternal rats with NP were randomly divided into 2 groups （n= 24 each） using a random number table： NP1 group and NP2 group. Forty-eight F1 generation rats of normal maternal rats were randomly divided into 2 groups （n= 24 each） using a random number table： s1 group and S2 group. The F1 generation rats were cross-fed immediately after birth between group NP2 and group S2 , and fed by their own mother rats in NP1 and S1 groups. All the offspring rats were fed to 21 days after birth by the maternal rats selected, and separately fed to 30 days after birth, and then subjected to behavioral testing. Retrieving and licking pups were recorded after delivery in maternal rats to evaluate the maternal behaviors. The mechanical and thermal paw withdrawal thresholds were measured in the offspring rats. Elevated plus maze and open field tests were conducted to detect anxiety and depression behaviors in the offspring rats. At 1 day after completion of behavioral testing, the expression of DNA methyhransferase 1 （DNMT1） and DNA methyltransferase 3a and 3b in the amygdala was detected by Western blot analysis. Results Com- pared with S1 or S2 groups, the latency to lick pups, latency to retrieve pups, and total retrieval time were significantly prolonged, and the total time spent licking pups was significantly shortened in NP1 group or NP2 group （P〈0.05 or 0.01）. There was no significant difference in the mechanical and thermal paw with- drawal thresholds in the offspring rats between the four groups （P〉0.05）. Compared with group S1, the ratios of time spent in the open arm to the closed arm and of time spent in the central square to the peripheral square were significantly decreased, DNMT1 expression in the amygdala was significantly up-regulated, and the total DNA methylation was increased in the offspring rats in S： and NP1 groups （P〈0.05）. Compared with group NP2 , the ratios of time spent in the open arm to the closed arm and of time spent in the central square to the peripheral square were significantly decreased, DNMT1 expression in the amygdala was significantly up-regulated, and the total DNA methylation was increased in the offspring rats in S2 and NP1 groups （P〈0.05）. Conclusion Decreased maternal behaviors in the rats with NP results in negative emotions including anxiety and depression in the offspring rats, and the mechanism is related to increased DNA methylation in the amygdala of the offspring rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2016年第7期831-834,共4页
Chinese Journal of Anesthesiology
基金
湖南省科学技术厅一般项目（2013SK3006）
