志不安于肾和魄不安于肺不寐大鼠脑γ-氨基丁酸变化的机制  

Mechanism of the brain GABA between insomnia rats of zhi unrest in the kidney and po unrest in the lung

作　　者：闫德祺 张星平 梁瑞宁 张文慧 王冠英 邓宁 刘涛 梁政亭 陈旭 YAN Deqi;ZHANG Xingping;LIANG Ruining;ZHANG Wenhui;WANG Guanying;DENG Ning;LIU Tao;LIANG Zhengting;CHEN Xu(The Fourth Clinical Medical College of Xinjiang Medical University(The Fourth Affiliated Hospital of Xinjiang Medical University),Urumqi 830017,China)

机构地区：[1]新疆医科大学第四临床医学院(新疆医科大学第四附属医院),乌鲁木齐830017

出　　处：《中华中医药杂志》2024年第9期4909-4914,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82160873,No.81960837,No.81560762);新疆自然科学基金重点项目(No.2022D01D48);新疆维吾尔自治区中医学重点学科(No.1005);新疆医科大学博士研究生创新创业项目(No.CXCY2021023),新疆医科大学第四附属医院博士后专项(No.ZYY2019BSH2)。

摘　　要：目的:比较志不安于肾和魄不安于肺不寐大鼠脑谷氨酸(Glu)、γ-氨基丁酸(GABA)、谷氨酸脱羧酶(GAD)、γ-氨基丁酸转运体(GAT)通路分子水平的差异。方法:将36只雄性SD大鼠随机分为正常组、志不安于肾组、魄不安于肺组,每组12只。正常组正常饲养,志不安于肾组以“久坐湿地,强力入水”法、魄不安于肺组以水平台法分别干预42 d制备不寐模型。以红外夜视摄像机观察大鼠白天觉醒次数和觉醒时间,以戊巴比妥钠诱导大鼠睡眠的潜伏期和睡眠时间作为睡眠评价指标,以水迷宫实验评价学习记忆功能,以酶联免疫吸附试验(ELISA)检测大鼠中段脑Glu和GABA水平,以免疫组化法检测大鼠中段脑GAD和GAT的水平。结果:魄不安于肺组白天起身走动次数增多,志不安于肾组下午处于不停的活动状态,提示单一主诉睡眠轻浅易醒及早醒分别复制成功。与正常组比较,两模型组睡眠时间均显著缩短(P<0.01),睡眠潜伏期显著延长(P<0.01);与正常组比较,两模型组第2、3、4天学习过程中逃避潜伏期显著延长(P<0.01),穿台次数显著减少(P<0.01);与正常组比较,两模型组中段脑GABA和Glu均显著下降(P<0.01),且志不安于肾组显著低于魄不安于肺组(P<0.01)。与正常组比较,两模型组各个脑区GAD表达均下降,且志不安于肾组部分脑区GAD表达显著低于魄不安于肺组(P<0.01);志不安于肾组各个脑区GAT表达均显著升高,魄不安于肺组部分脑区GAT表达显著升高,且魄不安于肺组各个脑区GAT表达显著低于志不安于肾组(P<0.01)。结论:志不安于肾和魄不安于肺不寐脑GABA下降和Glu升高的程度不同,与GAD下降及GAT升高的程度有关,说明志不安于肾不寐和魄不安于肺不寐二者差异的机制与GABA通路分子水平的变化有关。Objective:To compare the molecular levels of the brain gamma aminobutyric acid(GABA),glutamic acid(Glu),glutamic acid decarboxylase(GAD)and gamma-aminobutyric acid transporter(GAT)between insomnia rats with zhi unrest in the kidney and po unrest in the lung.Methods:A total of 36 male SD rats were randomly distributed into 3 groups,with 12 rats in each group.Normal group was raised normally.Zhi unrest in the kidney group(kidney group)and po unrest in the lung group(lung group)were intervened with‘long time sitting on the wet land and forced into water'or platforms in the water methods separately for 42 d.The number and time of awakening in the daytime of rats were observed with infrared video,the latency and time of sleep induced by pentobarbital sodium were used as sleep evaluation indicators,the learning and memory function was evaluated with water maze test,the Glu and GABA levels in the middle brain of rats were detected with enzyme-linked immunosorbent assay(ELISA),and the GAD and GAT levels in the middle brain of rats were detected with immunohistochemistry.Results:The number of times of getting up and walking in the lung group increased during the day,and kidney group was in an active state in the afternoon,suggesting that the single chief complaint of easy awakening and early awakening were successfully replicated.Compared with the normal group,the sleep time in the kidney group and the lung group was shorter(P<0.01),and the sleep latency was longer(P<0.01);The escape latency was prolonged(P<0.01)and the number of times of crossing the plaform was significantly reduced(P<0.01);GABA and Glu in the middle brain of the two model groups decreased significantly,with kidney group decreased more(P<0.01).The expression of GAD in several brain regions of the two model groups decreased,and the expression of GAD in the kidney group decreased more(P<0.01);The expression of GAT in several brain regions in the kidney group was significantly increased,while that in some brain regions in the lung group was significantly

关 键 词：水平台 久坐湿地 不寐 志不安于肾 魄不安于肺 Γ-氨基丁酸 机制 

分 类 号：R285.5[医药卫生—中药学]