补中益气安神汤对脾虚失眠大鼠CREB/BDNF/TrkB信号通路的影响  

Effects of Buzhong Yiqi Anshen Decoction on CREB/BDNF/TrkB Signaling Pathway of Insomnia with Spleen Deficiency in Rats

作　　者：李静[1] 郑柳怡 黄惠琼 陈晓东[1] 甘海宁 王丽[1] 朱蓓蓓 黄雪君[3,4] LI Jing;ZHENG Liuyi;HUANG Huiqiong;CHEN Xiaodong;GAN Haining;WANG Li;ZHU Beibei;HUANG Xuejun(Huizhou Traditional Chinese Medicine Hospital,Huizhou,Guangdong 516000,China;Guangzhou University of TCM,Guangzhou,Guangdong 510006,China;Guangdong Second Traditional Chinese Medicine Hospital,Guangzhou,Guangdong 510095,China;Guangdong Provincial Key Laboratory of Research and Development in TCM.Guangzhou,Guangdong 510095,China)

机构地区：[1]惠州市中医医院,广东惠州516000 [2]广州中医药大学,广东广州510006 [3]广东省第二中医院,广东广州510095 [4]广东省中医药研究开发重点实验室,广东广州510095

出　　处：《今日药学》2021年第11期834-838,843,共6页Pharmacy Today

基　　金：广东省中医药局科研项目(20201363);广东省传承发展中医药事业中医药人才培养项目[粤中医办函(2018)5号]。

摘　　要：目的观察补中益气安神汤(BZYQAS)对脾虚证失眠脑肠轴CREB/BDNF/TrkB信号通路的影响。方法将大鼠随机分为8组:正常组,模型组,百乐眠组,地西泮组补中益气汤组,补中益气安神汤高、中、低剂量组,每组10只。除正常组外,各组大鼠采用复合造模法[隔日禁食,大黄水煎液灌胃、腹腔注射对氯苯丙氨酸(PCPA)]复制大鼠脾虚型失眠证候模型。造模第3周开始给药,给药2周后检测大鼠大脑BDNF、GABA和5-HT以及血清中TNF-α和IL-1β含量;Western blotting法检测大鼠大脑和结肠中CREB、BDNF以及TrkB的表达。结果与模型组相比,补中益气安神汤能改善脾虚型失眠证候模型大鼠睡眠时间,显著性增加大脑BDNF、GABA以及5-HT含量(P<0.01,P<0.05)并降低血清TNF-α、IL-1β含量(P<0.01,P<0.05);显著性上调大脑CREB/BDNF/TrkB蛋白表达(P<0.01,P<0.05),并抑制结肠中CREB/BDNF/TrkB蛋白表达(P<0.01或P<0.05)。结论补中益气安神汤治疗脾虚失眠可能与上调大脑CREB/BDNF/TrkB信号通路相关因子表达,并抑制该通路在结肠中的表达有关。OBJECTIVE To observe the effect of Buzhong Yiqi Anshen decoction(BZYQAS) on CREB/BDNF/TrkB signal pathway of brain gut axis in insomnia of heart spleen deficiency syndrome. METHODS Rats were randomly divided into normal group, model group, Bailemian group, diazepam group, Buzhong Yiqi decoction group, and BZYQAS high-dose, medium-dose and low-dose groups, with 10 rats in each group.Except for the normal group, rats in each group were simulated by compound modeling method with fasting every other day, gavage of rhubarb decoction and injecting intraperitoneally with p-chlorphenoxyacetic acid(PCPA) to replicate the insomnia syndrome model of spleen deficiency in SD rats.The rats were given the drug from the third week of modeling.After 2 weeks of administration, the levels of BDNF,GABA and 5-HT in brain and TNF-α and IL-1β in serum were detected by ELISA.The expressions of CREB,BDNF and TrkB in brain and colon were detected by Western blotting. RESULTS Compared with the model group, BZYQAS could significantly improved the insomnia performance of rats with spleen deficiency syndrome, and significantly increased brain BDNF,GABA,and 5-HT contents(P<0.01,P<0.05) and decreased serum TNF-α and IL-1β contents(P<0.01,P<0.05).The protein expression of CREB/BDNF/TrkB in brain were significantly up-regulated(P<0.01,P<0.05),and the expression of CREB/BDNF/TrkB protein in colon were inhibited(P<0.01,P<0.05). CONCLUSION The possible mechanism of BZYQAS decoction in the treatment of insomnia with spleen deficiency is related to the up-regulation of CREB/BDNF/TrkB signaling pathway in brain but inhibition in colon.

关 键 词：补中益气安神汤 脾虚失眠 脑肠轴 CREB BDNF TRKB 

分 类 号：R285.5[医药卫生—中药学]