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目的评价咪达唑仑对慢性心理应激大鼠行为、神经内分泌激素水平及延髓腹外侧区心血管中枢内皮素-1(ET-1)mRNA表达的影响。方法雄性SD大鼠40只,体重150-200 g,行心理应激训练:先经7 d适应期(25 min／d暗盒适应)后,进入7 d复合应激期(给予不规则光-电刺激训练),最后进入1 d慢性心理应激期。实验大鼠随机分为5组(n=8),NS正常对照组和M正常对照组:在实验中仅接受25 min／d暗盒适应,分别于最后1 d暗适应前10min腹腔注射生理盐水1 ml和含咪达唑仑1．5 mg·kg-1的生理盐水溶液1 ml;根据刺激前10 min给予不同干预措施分为3组:安慰剂对照组、低剂量M实验组和高剂量M实验组,分别于刺激前10min腹腔注射生理盐水1 ml、含咪达唑仑0．75、1．5 mg·kg-1的生理盐水溶液1 ml。观察大鼠应激训练过程中行为的变化,实验结束后进行旷场行为测定并检测大鼠血浆促肾上腺皮质激素(ACTH)、皮质酮(CORT)浓度,原位杂交法检测延髓腹外侧区心血管中枢ET-1 mRNA的表达。结果与两正常对照组相比,安慰剂对照组行为评分增高,实验结束探查行为次数减少,ACTH和CORT浓度增高,延髓腹外侧区ET-1 mRNA表达下调;与安慰剂对照组相比,高剂量M实验组行为评分降低,低剂量和高剂量M实验组ACTH和CORT浓度均降低,ET-1 mRNA的表达均上调。结论咪达唑仑可减轻慢性心理应激引起的大鼠行为及神经内分泌的改变,并一定程度地抑制慢性心理应激诱发的延髓腹外侧区ET-1 mRNA的表达下调。
Objective To evaluate the effects of midazolam on behavior, neuroendocrine hormone levels and the expression of endothelin-1 (ET-1) mRNA in the rostral ventrolateral medulla after chronic psychological stress in rats. Methods Forty male Sprague-Dawley rats weighing 150-200 g were subjected to psychological stress training. After seven days of adaptation (25 min / d cassette adaptation), they were exposed to combined stress for 7 days (Irregular light- Stimulation training), and finally into the 1 d chronic psychological stress. The experimental rats were randomly divided into 5 groups (n = 8), NS normal control group and M normal control group: only 25 min / d cassette adaptation was performed in the experiment, and normal saline 1 ml and saline containing 1.5 mg · kg-1 midazolam 1 ml. According to different interventions 10 min before stimulation, the rats were divided into 3 groups: placebo control group, low-dose M group and high-dose M group In the experimental group, 1 ml of normal saline was injected intraperitoneally 10 min before stimulation, and 1 ml of physiological saline solution containing midazolam 0.75 and 1.5 mg · kg-1 respectively. The behavioral changes of rats during stress training were observed. After the experiment, the open-field behaviors were measured and the levels of ACTH and CORT in rats were measured. In situ hybridization was used to detect the extracellular center Expression of ET-1 mRNA in vascular center. Results Compared with the two normal control groups, the behavior scores of placebo control group increased, the number of exploration activities decreased, the concentrations of ACTH and CORT increased, and the expression of ET-1 mRNA decreased in rostral ventrolateral medulla. Compared with placebo control group, The behavioral score decreased in the experimental group at dose M, and the concentrations of ACTH and CORT in both low and high dose M groups were decreased, and the expression of ET-1 mRNA was up-regulated. Conclusion Midazolam can alleviate the behavioral and neuroendocrine changes induced by chronic psychological stress and inhibit the down-regulation of ET-1 mRNA expression in the rostral ventrolateral medulla induced by chronic psychological stress.