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Study on the protective effect and mechanism of Xiaoxuming Decoction on the brain of rats after cardiopulmonary resuscitation
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DOI   10.11656/j.issn.1672-1519.2021.04.23
Key Words   Xiaoxuming Decoction;cardiopulmonary resuscitation;oxidative stress;Kelch-like ECH-associated protein1;NF-E2-related factor 2;heme oxygenase-1
Author NameAffiliation
ZHOU Shenghua The Second Affiliated Hospital of Henan Chinese Medicine University, Zhengzhou 450046, China 
LI Hua The Second Affiliated Hospital of Henan Chinese Medicine University, Zhengzhou 450046, China 
GUO Yanke The Second Affiliated Hospital of Henan Chinese Medicine University, Zhengzhou 450046, China 
ZHANG Guoni Anyang Traditional Chinese Hospital, Anyang 455000, China 
Abstract
    [Objective] To study the protective effect and mechanism of Xiaoxuming Decoction on the brain of rats after cardiopulmonary resuscitation.[Methods] Sixty-three male SD rats of SPF grade were randomly divided into control group (8 rats) and modeling group (55 rats). The model rats were used the percutaneous epicardial electrical stimulation method to establish a rat cardiac arrest model. The successfully modeled rats were subjected to cardiopulmonary resuscitation. When the rat resumes spontaneous circulation,the rat cardiopulmonary resuscitation model was successfully established. The rats successfully modeled were randomly divided into 5 groups:Xiaoxuming Decoction high,medium and low dose group,dimethyl sulfoxide (DMSO) group and model group. After 10 minutes of cardiopulmonary resuscitation,rats in the Xiaoxuming Decoction high,medium,and low dose group were intra-gastrically administered with 300,150,75 mg/kg Xiaoxuming Decoction. The DMSO group was intra-gastrically administered with 100 mg/kg DMSO. The model group and the control group were intra-gastrically administered with equal volume of normal saline,once a day for 7 days. Scored the neurological function of rats before and after treatment. Observe the hippocampal lesions of rat brain tissue by hematoxylin-eosin (HE) staining. The content of lipid peroxide malondialdehyde (MDA) and superoxide dismutase (SOD) in rat hippocampus tissues were measured by enzyme-linked immunosorbent assay (ELISA). Detection of cytoplasmic protein chaperones (Keap1),nuclear factor E2 related factors (Nrf2) and heme oxygenase 1 (HO-1) mRNA expression levels in rat hippocampus tissues by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Detection of Keap1,Nrf2 and HO-1 expression levels protein in rat hippocampus tissues were detected by Western Blot.[Results] The neurological function scores of rats after treatment in the model group was higher than the control group (P<0.05),and the DMSO group and the Xiaoxuming Decoction high,medium and low dose group were lower than the model group (P<0.05). Neurons in the hippocampus of the control group without obvious lesions. In the model group,the arrangement of neurons was sparse and messy,the neurons were obviously edema,the nucleus was swollen,and the cytoplasm was vacuolated. The lesions in the DMSO group,Xiaoxuming Decoction high,medium and low dose groups were all improved. The content of MDA in the hippocampus tissues of rats in the model group was higher than that in the control group (P<0.05),while the DMSO group and Xiaoxuming Decoction high,medium and low dose group were lower than the model group (P<0.05). The SOD content in the model group was lower than that in the control group (P<0.05),and the DMSO group and the Xiaoxuming Decoction high,medium and low dose group were higher than the model group (P<0.05). The Keap1 mRNA and protein relative expression levels in the model group were lower than those in the control group (P<0.05),and the DMSO group and the Xiaoxuming Decoction high,medium and low dose group were lower than the model group (P<0.05). The Nrf2 and HO-1 mRNA and protein relative expression levels in the model group were higher than those in the control group (P<0.05),the DMSO group and Xiaoxuming Decoction high,medium and low dose group were all higher than the model group (P<0.05).[Conclusion] Xiaoxuming Decoction can improve the nerve function of cardiopulmonary resuscitation rats,reduce brain hippocampus tissue damage,and inhibit oxidative stress. It is speculated that the mechanism may be related to the activation of Keap1-Nrf2/HO-1 signaling pathway,down-regulation of Keap1 mRNA and protein expression,and up-regulation of Nrf2 and HO-1 mRNA and protein expression levels are related.

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