Shengmaisan combined with Liuwei Dihuang Decoction alleviates chronic intermittent hypoxia-induced cognitive impairment by activating the EPO/EPOR/JAK2 signaling pathway  

作　　者：SI Jianchao CHEN Xue QI Kerong LI Dongli LIU Bingbing ZHENG Yuying JI Ensheng YANG Shengchang 

机构地区：[1]Department of Physiology,Hebei University of Chinese Medicine,Shijiazhuang 050000,China [2]Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine,Shijiazhuang 050000,China [3]Department of Geriatrics,First People’s Hospital of Xiaogan,Xiaogan 432000,China

出　　处：《Chinese Journal of Natural Medicines》2024年第5期426-440,共15页中国天然药物（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.82274617);the Hebei Natural Science Foundation(Nos.H2022423352,H2022423370);the Fundamental Research Funds for the Provisional Universities of Hebei University of Chinese Medicine(No.YXTD2021005);Yanzhao Medical Research Project of Hebei University of Chinese Medicine(No.YZZY2022004);the Graduate Innovation Fund of Hebei University of Chinese Medicine(No.XCXZZSS2021005)。

摘　　要：Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the kidneys.This study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by CIH.We exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH session.Additionally,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular injection.Cognitive function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron microscopy.Oxidative stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western blotting.To further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 h.Our results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in mice.Specifically,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling pathway.Conversely,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH conditions.These findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.

关 键 词：Chronic intermittent hypoxia Cognitive impairment Shengmaisan Liuwei Dihuang Decoction Oxidative stress EPO/EPOR/JAK2 signaling pathway 

分 类 号：R285[医药卫生—中药学]