摘要
目的探讨野黄芩苷对卒中后抑郁(PSD)模型大鼠糖原合成酶激酶3β(GSK-3β)/β-连环蛋白(β-catenin)信号通路的影响。方法用线栓法制备大鼠脑卒中模型,待脑卒中模型制备成功后,用孤养结合慢性温和不可预知应激(CUMS)建立抑郁模型。将模型大鼠按体重随机分为模型组,低、中、高剂量实验组和阳性对照组,每组10只;另取10只正常大鼠作为阴性对照组。在PSD造模第3周后开始进行干预,阴性对照组和模型组均按1.5μL·g^(-1)的剂量灌胃给予0.9%Na Cl;低、中、高剂量实验组按10 mg·kg^(-1)的剂量分别灌胃给予10,20和40 mg·mL^(-1)野黄芩苷;阳性对照组灌胃给予10 mg·kg^(-1)盐酸氟西汀胶囊。6组大鼠每天给药1次,均连续给药21 d。用Morris水迷宫实验检测大鼠空间学习记忆能力,用Western blot法检测大鼠海马组织中Wnt、GSK-3β和β-catenin水平,用酶联免疫吸附实验法检测海马组织中5-羟色胺(5-HT)和去甲肾上腺素(NE)水平。结果低、高剂量实验组和阳性对照组、模型组、阴性对照组的目标象限游泳时间分别为(19.73±1.27),(24.68±2.37),(24.79±3.42),(13.08±31.62)和(29.53±3.41) s,Wnt蛋白相对表达量分别为0.45±0.07,1.04±0.10,1.01±0.08,1.15±0.13和1.02±0.13,GSK-3β蛋白相对表达量分别为0.49±0.05,0.82±0.07,0.85±0.07,0.41±0.03和0.94±0.10,β-catenin蛋白相对表达量分别为0.43±0.07,0.64±0.06,0.66±0.10,0.38±0.05和0.77±0.07,5-HT分别为(134.90±10.38),(168.26±15.51),(167.84±24.68),(118.62±15.71)和(190.26±19.52)ng·mL^(-1),NE分别为(253.57±29.42),(355.70±61.82),(360.13±49.70),(207.62±31.54)和(438.41±51.67) ng·mL^(-1),低、高剂量实验组和阳性对照组的上述指标与模型组比较,差异均有统计学意义(均P <0.05)。结论野黄芩苷通过激活GSK-3β/β-catenin信号通路,抑制海马神经细胞凋亡,从而发挥治疗PSD的作用。
Objective To investigate the effect of scutellarin on hippocampal neurogenesis and glycogen synthase kinase-3(GSK-3β)/β-catenin signaling pathway in rats with post-stroke depression.Methods The rat stroke model was prepared by the suture method,and the depression model was established by solitary combined with chronic unpredictable mild stress(CUMS) after the stroke model successfully established.According to body weight,the model rats were randomly divided into model group,experimental-L,-M,-H groups and positive control group with 10 cases per group.Another 10 normal rats were taken as the negative control group.Intervention was started after 3 weeks of post-stroke depression(PSD) modeling,the negative control and model groups were given 0.9% NaCl by intragastric administration at a dose of 1.5 μL·g^(-1);the experimental-L,-M,-H groups were given 10,20 and 40 mg·mL^(-1) scutellarin at the dose of 10 mg·kg^(-1) by intragastric administration;the positive control group was given fluoxetine hydrochloride capsules 10 mg·kg^(-1) by intragastric administration.Six groups were administered once a day for 21 days.Detection of spatial learning and memory ability in rats by Morris water maze test.The levels of Wnt,GSK-3β and β—catenin in the hippocampus tissue were detected by Western blot method.The levels of 5-hydroxytryptamine(5-HT) and norepinephrine(NE) in the hippocampus tissue were detected by enzyme linked immunosorbent assay.Results The target quadrant swimming time in the experimental-L,-H groups and positive control group,negative control group,model group were(19.73±1.27),(24.68±2.37),(24.79±3.42),(13.08±31.62) and(29.53±3.41) s,relative expression levels of Wnt were 0.45±0.07,1.04±0.10;1.01±0.08 1.15±0.13 and 1.02±0.13,relative expression levels of GSK-3β were 0.49±0.05,0.82±0.07,0.85±0.07,0.41±0.03 and 0.94±0.10,relative expression levels of β-catenin were 0.43±0.07,0.64±0.06,0.66±0.10,0.38±0.05 and 0.77±0.07,5-HT were(134.90±10.38),(168.26±15.51),(167.84±24.68),(118.62±
作者
黎顺成
徐雪怡
刘向来
林春燕
LI Shun-cheng;XU Xue-yi;LIU Xiang-lai;LIN Chun-yan(Department of PsychiatryHainan Province Arming Hospital,Haikou 570206,Hainan Province,China;Department of Medical RehabilitationHainan Province Arming Hospital,Haikou 570206,Hainan Province,China;Department of Prevention Section,Hainan Province Arming Hospital,Haikou 570206,Hainan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第19期2596-2600,共5页
The Chinese Journal of Clinical Pharmacology
基金
海南省自然科学基金资助项目(819MS129)。
