| 引用本文: |
刘艳霞,李雁.扶正祛邪方加减治疗失眠症的药效及其对脑组织内GABA ARα1、5-HT1AR、mGluR7表达的影响[J].湖南中医药大学学报,2023,43(7):1149-1154[点击复制] |
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| 扶正祛邪方加减治疗失眠症的药效及其对脑组织内GABA ARα1、5-HT1AR、mGluR7表达的影响 |
| 刘艳霞,李雁 |
| (上海中医药大学附属市中医医院肿瘤科, 上海 200071) |
| 摘要: |
| 目的 探究扶正祛邪方加减对氯苯丙氨酸（para-chlorophenylalanine，PCPA）失眠模型小鼠的镇静催眠作用及其对脑组织内γ-氨基丁酸A受体α1（gamma-aminobutyric acid A receptor subtype α1，GABA ARα1）、5-羟色胺1A受体（5-hydroxytryptamine 1A receptor，5-HT1AR）、代谢型谷氨酸受体7（metabotropic glutamate receptor 7，mGluR7）表达的影响。方法 将50只小鼠随机分为空白对照组、模型组、艾司唑仑组、高剂量组和低剂量组，连续灌胃给药7 d后，各组小鼠进行戊巴比妥钠协同睡眠实验和旷场试验的行为学测试，分别采用RT-qPCR和Western blot法检测脑组织中GABA ARα1、5-HT1AR、mGluR7 mRNA和蛋白的表达以及mGluR7/GABA ARα1的比值。结果 与空白对照组比较，模型组小鼠睡眠潜伏期延长（P<0.05），睡眠时间缩短（P<0.05），旷场试验中总的区域路程延长（P<0.05），中心区停留时间缩短（P<0.05），脑组织中GABA ARα1、5-HT1AR mRNA和蛋白的表达均降低（P<0.05），mGluR7 mRNA和蛋白的表达升高（P<0.05），mGluR7/GABA ARα1上升（P<0.05）。与模型组比较，艾司唑仑组和高剂量组、低剂量组小鼠睡眠潜伏期缩短（P<0.05），睡眠时间延长（P<0.05），总的区域路程减少（P<0.05），中心区停留时间增加（P<0.05），脑组织中GABA ARα1、5-HT1AR mRNA和蛋白的表达上升（P<0.05），mGluR7 mRNA和蛋白表达降低（P<0.05），mGluR7/GABA ARα1下降（P<0.05）。与艾司唑仑组比较，高剂量组、低剂量组小鼠睡眠潜伏期和总区域路程增加（P<0.05），睡眠持续时间和中心区停留时间减少（P<0.05），GABA ARα1、5-HT1AR mRNA和蛋白表达下降（P<0.05）、mGluR7 mRNA和蛋白表达上升（P<0.05），mGluR7/GABA ARα1上升（P<0.05）。与高剂量组比较，低剂量组小鼠睡眠潜伏期、总区域路程增加（P<0.05），睡眠持续时间、中心区停留时间减少（P<0.05），GABA ARα1、5-HT1AR mRNA和蛋白表达下降（P<0.05）、mGluR7 mRNA和蛋白表达上升（P<0.05），mGluR7/GABA ARα1上升（P<0.05）。结论 扶正祛邪方加减可以改善PCPA失眠模型小鼠的睡眠，有较好的镇静催眠作用，其机制可能是通过调节脑组织内GABA ARα1、5-HT1AR、mGluR7水平发挥作用。 |
| 关键词: 扶正祛邪方加减 失眠 氯苯丙氨酸 γ-氨基丁酸A受体α1 5-羟色胺1A受体 代谢型谷氨酸受体7 |
| DOI：10.3969/j.issn.1674-070X.2023.07.001 |
| 投稿时间：2023-01-18 |
| 基金项目:国家自然科学基金面上项目（81973795，82174183）；上海申康医院发展中心临床三年行动计划资助项目（SHDC2020CR4052）。 |
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| Efficacy of modified Fuzheng Quxie Formula in treating insomnia and its influence on GABA ARα1, 5-HT1AR, and mGluR7 expressions in brain tissue |
| LIU Yanxia,LI Yan |
| (Department of Oncology, Municipal Chinese Medicine Hospital of Shanghai University of Chinese Medicine, Shanghai 200071, China) |
| Abstract: |
| Objective To explore the sedative and hypnotic effects of modified Fuzheng Quxie Formula (FZQXF) on insomnia model mice induced by para-chlorophenylalanine (PCPA) and its influence on gamma aminobutyric acid A receptor subtype α1 (GABA ARα1), 5-hydroxytryptamine 1A receptor (5-HT1AR), and metabotropic glutamate receptor 7 (mGluR7) expressions in brain tissue. Methods Fifty mice were randomly divided into blank control group, model group, estazolam group, high- and low-dose modified FZQXF groups. After 7 d of continuous intragastric administration, the mice in each group were subjected to behavioral tests including pentobarbital sodium synergistic sleep experiment and open field experiment. Meanwhile, the mRNA and protein expressions of GABA ARα1, 5-HT1AR, and mGluR7 in brain tissue and the ratio of mGluR7/GABA ARα1 were determined by RT-qPCR and Western blot, respectively. Results Compared with blank control group, the mice in model group showed prolonged sleep latency (P<0.05), shortened sleep time (P<0.05), longer total regional distance in the open field experiment (P<0.05), shorter residence time in the central area (P<0.05), lower mRNA and protein expressions of 5-HT1AR and GABA ARα1 in brain tissue (P<0.05), higher mRNA and protein expressions of mGluR7 (P<0.05), and increased mGluR7/GABA ARα1 ratio (P<0.05). Compared with model group, the mice in estazolam, high- and low-dose modified FZQXF groups showed shortened sleep latency (P<0.05), prolonged sleep time (P<0.05), reduced total regional distance (P<0.05), extended residence time in central area (P<0.05), higher mRNA and protein expressions of GABA ARα1 and 5-HT1AR in brain tissue (P<0.05), lower mRNA and protein expressions of mGluR7 (P<0.05), and increased mGluR7/GABA ARα1 ratio (P<0.05). Compared with estazolam group, the mice in high- and low-dose modified FZQXF groups showed prolonged sleep latency and total regional distance (P<0.05), shortened sleep time and residence time in central area (P<0.05), lower mRNA and protein expressions of GABA ARα1 and 5-HT1AR, higher mRNA and protein expressions of mGluR7 (P<0.05), and increased mGluR7/GABA ARα1 ratio (P<0.05). Compared with high-dose modified FZQXF group, the mice in low-dose modified FZQXF group showed longer sleep latency and total regional distance (P<0.05), shorter sleep time and residence time in central area (P<0.05), lower mRNA and protein expressions of GABA ARα1 and 5-HT1AR, and increased mGluR7/GABA ARα1 ratio (P<0.05). Conclusion Modified FZQXF can exert its sedative and hypnotic effects on PCPA-induced insomnia model mice, and its mechanism of sleeping-improving may be related to regulating the levels of GABA ARα1, 5-HT1AR and mGluR7 in brain tissue. |
| Key words: modified Fuzheng Quxie Formula insomnia para-chlorophenylalanine gamma-aminobutyric acid A receptor subtype α1 5-hydroxytryptamine 1A receptor metabotropic glutamate receptor 7 |
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