醒神解郁汤通过CyPA-ERK1/2-NF-κB信号通路调控神经炎症改善卒中后抑郁  

Xingshen Jieyu decoction regulates neuroinflammation through CyPA-ERK1/2-NF-κB signaling pathway to improve post-stroke depression

作　　者：郑国玉[1] 栗静媛 杨广军[3] 于存国[1] ZHENG Guo-yu;LI Jing-yuan;YANG Guang-jun;YU Cun-guo(Department of Traditional Chinese Medicine,Qinhuangdao Harbor Hospital,Qinhuangdao 066002;Department of Neurology,The First Hospital of Qinhuangdao,Qinhuangdao 066000;General Internal Medicine,Qinhuangdao Harbor Hospital,Qinhuangdao 066002,China)

机构地区：[1]秦皇岛市海港医院中医科,河北秦皇岛066002 [2]秦皇岛市第一医院神经内科,河北秦皇岛066000 [3]秦皇岛市海港医院综合内科,河北秦皇岛066002

出　　处：《解剖科学进展》2024年第4期349-353,共5页Progress of Anatomical Sciences

基　　金：国家自然科学基金(81973601);秦皇岛市重点研发计划科技支撑项目(201902A143)。

摘　　要：目的 基于CyPA-ERK1/2-NF-κB信号通路探讨醒神解郁汤改善卒中后抑郁的作用机制。方法 采用大脑中动脉缺血再灌注联合慢性温和性不可预见性应激压力的方法复制卒中后抑郁模型,造模成功后分别以醒神解郁汤低(8.19 g/kg)、中(16.38 g/kg)、高剂量(32.76 g/kg)灌胃14天,每天1次。Ayelet Levy神经功能评分、糖水消耗实验、旷场实验检测大鼠行为学变化;HE和Nissl染色观察大鼠海马区病理损伤和神经元损伤情况;免疫荧光染色检测小胶质细胞(Iba-1)、星形胶质细胞(GFAP)阳性表达;ELISA试剂盒测定大鼠脑组织中白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)、IL-10表达水平;Western blot检测大鼠脑组织中亲环素A(CyPA)、细胞外信号调节激酶1/2(ERK1/2)、p-ERK1/2及核转录因子-κB(NF-κB)蛋白表达水平。结果 醒神解郁汤能降低神经功能评分,提高糖水偏好指数、跨格次数和站立次数,减轻海马区病理损伤、增加神经元数量,降低Iba-1、GFAP表达量、IL-1β、IL-6、TNF-α表达水平,升高IL-10表达水平,降低CyPA、p-ERK1/2及NF-κB蛋白表达水平。结论 醒神解郁汤能够抑制卒中后抑郁大鼠神经炎症,改善神经功能,其作用机制可能与调控CyPA-ERK1/2-NF-κB信号通路有关。Objective To explore the mechanism of Xingshen Jieyu decoction improving post-stroke depression based on CyPA-ERK1/2-NF-κB signaling pathway. Methods Post-stroke depression was establishled in rats by middle cerebral artery ischemia-reperfusion combined with chronic mild unforeseeable stress. The rats were given Xingshen Jieyu decoction at low(8.19 g/kg), medium(16.38 g/kg)and high(32.76 g/kg)doses by intragastric administrationfor 14 d, once a day. Ayelet Levy neural function score, sugar and water consumption test and open field test were used to detect the behavioral changes of rats. The pathological damage and neuronal damage of rat hippocampus were observed by HE and Nissl staining. The positive expressions of Iba-1 and GFAP were detected by immunofluorescence staining. The levels of IL-1β, IL-6, TNF-α and IL-10 were analyzed by ELISA. The expressions of CyPA, ERK1/2, p-ERK1/2 and NF-κB were detected by Western blot. Results Xingshen Jieyu decoction can reduce nerve function score, improve sugar and water preference index, cross cell times and standing times, alleviate pathological injury in hippocampus, increase the number of neurons, reduce the expressions of Iba-1, GFAP, IL-1β, IL-6, TNF-α, and increase the level of IL-10, decrease the expressions of CyPA, p-ERK1/2 and NF-κB. Conclusion Xingshen Jieyu decoction can inhibit neuroinflammation and improve nerve function in post-stroke depression mice, and its mechanism of action may be related to the regulation of CyPA-ERK1/2-NF-κB signaling pathway.

关 键 词：卒中后抑郁 醒神解郁汤 神经炎症 CyPA-ERK1/2-NF-κB信号通路 

分 类 号：R749.7[医药卫生—神经病学与精神病学]