摘要
目的:观察归脾汤(GPD)对慢性睡眠剥夺模型大鼠多巴胺D2受体(D2R)及蛋白磷酸酶1(PP1)/环磷腺苷应答元件结合蛋白(CREB)信号通路的影响。方法:48只雄性SD大鼠随机分为正常组,模型组,艾司唑仑(0.009 mg/mL)组,GPD高、中、低剂量(1.86、0.93、0.47 g/mL)组,每组8只。除正常组外均采用改良多平台水环境法建立慢性睡眠剥夺模型,周期21 d。造模第15天开始,各治疗组连续灌胃给药7 d,观察大鼠一般状态,采用RT-PCR、Western Blot法检测各组D2R及PP1、CREB mRNA和蛋白的表达。结果:与正常组比较,大鼠造模后出现昼夜节律紊乱,精神倦怠,毛发枯燥,反应迟钝,海马D2R mRNA和蛋白表达升高(P<0.05,P<0.01),PP1、CREB mRNA和蛋白表达显著降低(P<0.05,P<0.01);与模型组比较,艾司唑仑组与GPD各剂量组大鼠昼夜节律紊乱和精神状况相对改善,毛发相对润泽,反应相对灵敏;GPD中剂量组D2R mRNA和蛋白表达降低(P<0.05,P<0.01),GPD中、低剂量组PP1 mRNA和蛋白显著升高(P<0.05,P<0.01),GPD中剂量组CREB蛋白表达升高(P<0.01)。结论:GPD具有较好改善慢性睡眠剥夺模型大鼠睡眠的作用,其机制可能与下调海马D2R表达,调控PP1/CREB信号通路有关。
Objective: To observe the effects of Guipi Decoction(GPD) on dopamine D2 receptor(D2R) and PP1/CREB signaling pathway in chronic sleep deprivation rats. Methods: Forey-eight male SD rats were randomly divided into normal group, model group, estazolam(0.009 mg/mL) group, GPD high-dose, medium-dose and low-dose(1.86, 0.93, 0.47 g/mL) groups,8 rats in each group. Except for the normal group, the modified multiple-platform method was used to establish the chronic sleep deprivation model, and the cycle was 21 days. From the 15th day, each treatment group was given ingastric administration for 7 days continuously. The general status of rats was observed, and the expression of D2R, PP1 and CREB mRNA and protein in each group was detected by RT-PCR and Western Blot. Results: Compared with the normal group, after modeling, the rats showed circadian rhythm disorder, mental burnout, hair boring, slow response, D2R mRNA and protein expression increased(P<0.05, P<0.01), PPI, CREB mRNA and protein expression decreased(P<0.05, P<0.01). Compared with model group, the rats in Esazolam group and GPD groups had better circadian rhythm disorder and mental condition, and their hair was more moist and responsive. The expressions of D2R mRNA and protein in GPD medium-dose group were decreased(P<0.05, P<0.01), PP1mRNA and protein in GPD medium-dose and low-dose groups were significantly increased(P<0.05, P<0.01), and the expression of CREB mRNA and protein in GPD medium-dose group was significantly increased(P<0.01). Conclusion: GPD has a good effect on improving sleep in rats with chronic sleep deprivation, and its mechanism may be related to inhibiting hippocampal D2R expression and regulating PP1/CREB pathway.
作者
张敏
黄俊山
张一帆
曾雪爱
王秀峰
陈铭奇
ZHANG Min;HUANG Jun-shan;ZHANG Yi-fan;ZENG Xue-ai;WANG Xiu-feng;CHEN Ming-qi(Fujian Academy of Chinese Medical Sciences,Fuzhou 350003,China;Fujian Key Laboratory of Sleep Medicine of Traditional Chinese Medicine,Fuzhou 350003,China;National Inheritance Office of Famous TCM Experts HUANG Jun-shan,Fuzhou 350003,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2022年第12期7050-7054,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家科技部重点研发计划项目(No.2018YFC1705600)
福建省自然科学基金面上项目(No.2019J01721)
福建省属公益类科研院所基本科研专项(No.2019R1003-3)。
