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目的:探讨天麻素对对氯苯丙氨酸(PCPA)致失眠小鼠睡眠的改善作用。方法:将KM小鼠随机分为正常对照组、模型对照组、天麻素10、20、40 mg/kg组、地西泮2.6 mg/kg组,除正常对照组外,其余各组采用腹腔连续注射2 d PCPA,建立失眠小鼠模型。造模成功后,各组灌胃给予相应药物,模型对照组及正常对照组灌胃给予相应体积生理盐水,连续6 d,每天称量小鼠体质量并记录其行为变化;第6 d末次给药后,观察腹腔注射戊巴比妥钠诱导小鼠的睡眠发生率、睡眠潜伏期及睡眠时间;苏木精-伊红染色法(HE)观察各组小鼠海马组织病理变化,酶联免疫吸附法(ELISA)检测各组小鼠大脑皮层5-羟色胺(5-HT)含量,蛋白免疫印迹法检测细胞外调节蛋白激酶(ERK)、磷酸化细胞外调节蛋白激酶(p-ERK)、B淋巴细胞瘤-2基因(BCL-2)、白细胞介素-1β(IL-1β)及白细胞介素-6(IL-6)蛋白表达的变化。结果:与正常对照组比较,模型对照组小鼠体质量下降,睡眠发生率下降,睡眠潜伏期延长,睡眠时间缩短(P<0.01),小鼠海马区部分神经元细胞胞核固缩深染,胞质溶解,大量锥体细胞排列紊乱,细胞体积明显变小,胞核固缩,小鼠大脑皮层中5-HT含量减少(P<0.01),IL-6蛋白表达、p-ERK/ERK比值明显升高(P<0.01),BCL-2、IL-1β蛋白表达显著下调(P<0.01);与模型对照组比较,天麻素10、20、40 mg/kg组小鼠体质量恢复,睡眠率升高,睡眠潜伏期缩短,睡眠时间延长(P<0.01),天麻素在一定程度上改善了大脑组织的病变程度,明显恢复脑组织中5-HT含量,明显逆转了IL-6、BCL-2、IL-1β蛋白表达以及p-ERK/ERK比值(P<0.05或P<0.01)。结论:天麻素对PCPA致失眠小鼠的睡眠具有显著的改善作用,其机制可能与调节脑内IL-6、IL-1β、BCL-2蛋白表达以及p-ERK/ERK比值有关。
Abstract：Objective: To investigate the effects of gastrodin on p-chlorophenylalanine(PCPA)-induced insomnia mice. Methods KM mice were randomized into normal control group, model group, 10, 20, and 40 mg/kg gastrodin groups, and 2.6 mg/kg diazepam group. Then, the mice, except for the normal control group, received(i.p.) PCPA for 2 consecutive days to induce insomnia. After modeling, mice in gastrodin groups were given(i.g.) corresponding drugs and mice in model group and normal control group the corresponding volume of normal saline for 6 days. The body weight and behavior changes were observed and recorded every day. After the last administration on the 6 th day, the sleep rate, sleep latency, and sleep duration of mice induced by pentobarbital sodium(i.p.) were observed. The pathological changes of hippocampus were detected by hematoxylin-eosin(HE) staining, the content of 5-hydroxytryptamine(5-HT) in cerebral cortex by enzyme linked immunosorbent assay(ELISA), and the expression of extracellular regulated protein kinase(ERK), phosphorylated extracellular signal-regulated protein kinase(p-ERK), B lymphoma-2 gene(Bcl-2), interleukin-1β(IL-1β), and interleukin-6(IL-6) by Western blotting. Results: Compared with the normal control group, the model group demonstrated reduced body weight and sleep rate, long sleep latency, short sleep duration(P<0.01), pyknosis of hyperchromatic nuclei in some neurons, cytoplasmic dissolution, a large number of disordered pyramidal cells, with decreased volume and karyopycnosis, reduced content of 5-HT in cerebral cortex(P<0.01), raised IL-6 expression and p-ERK/ERK ratio(P<0.01), and down-regulated expression of Bcl-2 and IL-1β(P<0.01). Compared with the model group, all gastrodin groups(10, 20, and 40 mg/kg) showed body weight recovery, increased sleep rate, short sleep latency, and long sleep duration(P<0.01). Gastrodin alleviated the lesion of brain tissue, significantly restored the content of 5-HT in brain tissue, and significantly reversed the expression of IL-6, Bcl-2, and IL-1β, and the p-ERK/ERK ratio(P<0.05 or P<0.01). Conclusion:Gastrodin can significantly improve the sleep of PCPA-induced insomnia mice, possibly by regulating the expression of IL-6, Bcl-2, and IL-1β in brain tissue and p-ERK/ERK ratio.
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基本信息:
DOI：10.13412/j.cnki.zyyl.2021.05.007
中图分类号:R285.5
引用信息:
[1]龙盼,胡晓霞,胡琦兰,等.天麻素对氯苯丙氨酸(PCPA)致失眠小鼠的镇静催眠作用研究[J].中药药理与临床,2021,37(05):33-38.DOI:10.13412/j.cnki.zyyl.2021.05.007.
基金信息:
NSFC-贵州喀斯特科学研究中心(编号：U1812403); 国家自然科学基金委员会-贵州省人民政府联合基金项目([2019]U1812403); 贵阳市科技计划项目(筑科合同[2017]30-25号); 贵州省高层次创新型人才百层次人才项目(贵州省科技厅黔科合人才[2015]4029号); 贵州医科大学药学国际科技合作基地(黔科合平台人才[2017]5802)
2021-10-15
2021-10-15