脑心安胶囊调节AMPK/GSK-3β/Nrf2信号通路对缺血性中风大鼠的神经保护作用*

作者：李 明，李 琦，罗佳晶，张佳诺，李 睿，吴圣贤

单位：北京中医药大学东直门医院，北京 100700

引用：引用：李明，李琦，罗佳晶，张佳诺，李睿，吴圣贤.脑心安胶囊调节AMPK/GSK-3β/Nrf2信号通路对缺血性中风大鼠的神经保护作用[J].中医药导报,2026,32(1):77-81,97.

DOI：10.13862/j.cn43-1446/r.2026.01.012

PDF： 下载PDF

摘要：

目的：基于腺苷酸活化蛋白激酶（AMPK）/糖原合成酶激酶3β（GSK-3β）/核因子E2相关因子2（Nrf2）信号通路探讨脑心安胶囊对缺血性中风大鼠的神经保护作用机制。方法：采用线栓法建立缺血性中风大鼠模型，将大鼠分为假手术组（Sham组，不插入栓线）、模型组（M组）、脑心安胶囊组（脑心安组，0.72 g/kg）、AMPK激活剂（AICAR）组（100 mmol/L）、脑心安（0.72 g/kg）+AMPK抑制剂[Compound C（CC），20 μmol/L]组。对神经功能损伤进行评分；TTC染色检测脑梗死体积；微量法检测超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）水平；TUNEL染色检测脑组织细胞凋亡；免疫组化法检测巢蛋白（Nestin）、神经生长因子（NGF）蛋白表达；蛋白质印迹（Western blotting）法检测AMPK/GSK-3β/Nrf2信号通路相关蛋白表达。结果：与Sham组比较，M组大鼠神经功能损伤评分、脑梗死体积、脑组织MDA水平、细胞凋亡率、Nestin及NGF蛋白表达明显上升，SOD、GSH-Px活性及p-AMPK、p-GSK-3β、Nrf2表达水平明显下降（P<0.05）；与M组比较，AICAR组、脑心安组神经功能损伤评分、脑梗死体积、脑组织MDA水平、细胞凋亡率明显下降，SOD、GSH-Px活性及Nestin、NGF、p-AMPK、p-GSK-3β、Nrf2蛋白表达明显上升（P<0.05）；与脑心安组比较，脑心安+CC组神经功能损伤评分、脑梗死体积、脑组织MDA水平、细胞凋亡率明显上升，SOD、GSH-Px活性及Nestin、NGF、p-AMPK、p-GSK-3β、Nrf2蛋白表达明显下降（P<0.05）。结论：脑心安胶囊可以抑制缺血性中风大鼠的氧化应激，减少脑组织细胞凋亡，发挥神经保护作用，其机制可能与激活AMPK/GSK-3β/Nrf2信号通路有关。

关键词：缺血性中风；脑心安胶囊；腺苷酸活化蛋白激酶/糖原合成酶激酶3β/核因子E2相关因子2信号通路；神经保护；大鼠

Abstract：

Objective: To investigate the neuroprotective mechanism of Naoxin'an capsule in rats with ischemic stroke based on the AMP-activated protein kinase (AMPK)/glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Methods: A rat model of ischemic stroke was established by the filament occlusion method. The rats were divided into the sham-operated group (no filament insertion), model group, Naoxin'an capsule group (0.72 g/kg), AMPK activator (AICAR) group (100 mmol/L), and Naoxin'an (0.72 g/kg) + AMPK inhibitor [Compound C (CC), 20 μmol/L] group. Neurological deficit scores were assessed. Cerebral infarction volume was measured by TTC staining. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were detected using a microplate assay. Apoptosis in brain tissue was detected by TUNEL staining. The protein expression of nestin and nerve growth factor (NGF) was detected by immunohistochemistry. The protein expression related to the AMPK/GSK-3β/Nrf2 signaling pathway was detected by Western blotting. Results: Compared with the sham-operated group, the model group showed significantly increased neurological deficit scores, cerebral infarction volume, MDA levels, apoptosis rate, and expression of nestin and NGF protein, while the activities of SOD and GSH-Px and the expression levels of p-AMPK, p-GSK-3β, and Nrf2 were significantly decreased in sham-operated group (P<0.05). Compared with the model group, the AICAR group and Naoxin'an group showed significantly decreased neurological deficit scores, cerebral infarction volume, MDA levels, and apoptosis rate, while the activities of SOD and GSH-Px and the expression levels of nestin, NGF, p-AMPK, p-GSK-3β, and Nrf2 were significantly increased in AICAR group and Naoxin'an group (P<0.05). Compared with the Naoxin'an group, the Naoxin'an+CC group showed significantly increased neurological deficit scores, cerebral infarction volume, MDA levels, and apoptosis rate, while the activities of SOD and GSH-Px and the expression levels of nestin, NGF, p-AMPK, p-GSK-3β, and Nrf2 were significantly decreased in Naoxin'an+CC group (P<0.05). Conclusion: Naoxin'an capsule can inhibit oxidative stress, reduce apoptosis in brain tissue, and exert neuroprotective effects in rats with ischemic stroke, the mechanism of which may be related to the activation of the AMPK/GSK-3β/Nrf2 signaling pathway.

Key words：ischemic stroke; Naoxin'an capsule; AMP-activated protein kinase/glycogen synthase kinase-3β/nuclear factor erythroid 2-related factor 2 signaling pathway; neuroprotection; rat

发布时间：2026-01-30

点击量：0