中药药理与临床2025，Vol.41Issue(1)：22-28,7.
六味地黄苷糖对SARS-CoV-2刺突蛋白所致神经损伤的保护作用
Liuwei Dihuang(六味地黄)Active Fraction Combination Protects against SARS-CoV-2 Spike Protein-Induced Nervous System Injury
摘要
Abstract
Objective:To study the effects and potential pathways of Liuwei Dihuang(六味地黄)Active Fraction Combination(LW-AFC)in a-meliorating nervous system damage caused by the spike protein of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Meth-ods:Thirty-four C57/6J mice were assigned into normal control,model control,and LW-AFC(1.6 g/kg)groups based on body weight and spontaneous activity.The mice in the LW-AFC group were administrated with 1.6 g/kg LW-AFC by gavage,while those in the model control group and normal control group were administered with the same volume of deionized water.After 7 days of preventive treatment,the model control group and LW-AFC(1.6 g/kg)group received a single tail vein injection of the spike protein for modeling,while the normal control group was injected with an equal volume of normal saline.After 28 days of gavage treatment(i.e.,35 days of administration),the rotarod test was carried out to assess the motor ability of mice,and the open field and marble burying tests were conducted to evaluate the anxiety-like be-havior.The tail suspension test was conducted to assess the depressive-like behavior,and the novel object recognition test was carried out to evaluate the learning and memory capabilities.Immunofluorescence was used to detect the number of fluorescent-positive cells for ionized cal-cium-binding adaptor molecule 1(Iba-1)and neuronal nuclei(NeuN)in the hippocampus.Hematoxylin-eosin staining was performed to as-sess the pathological damage in the lung tissue.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of inter-leukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in the hippocampal tissue.Results:Compared with the normal control group,the model control group showed a decrease in the rod holding time(P<0.01),an increase in the number of buried marbles(P<0.01),a de-crease in the number of entries into the central area(P<0.05),and no significant differences in the indicators of the tail suspension test.In addition,the model control group showed increases in the lung tissue damage score(P<0.01)and the number of Iba-1-positive cells in the hippocampus(P<0.01),a decrease in the number of NeuN-positive cells(P<0.05),and rises in the levels of IL-6 and TNF-α in the hippo-campus(P<0.01).Compared with the model control group,the LW-AFC(1.6 g/kg)group showed an increase in the rod holding time(P<0.05),a decrease in the number of buried marbles(P<0.05),and no significant changes in the indicators of open field and tail suspension tests.Moreover,LW-AFC(1.6 g/kg)decreased the score of lung tissue injury(P<0.05)and the number of Iba-1-positive cells in the hip-pocampus(P<0.05),increased the number of NeuN-positive cells(P<0.05),and lowered the levels of IL-6 and TNF-α in the hippocampal tissue(P<0.05).Conclusion:LW-AFC has a preventive and therapeutic effect of the spike protein-induced motor ability reduction,anxiety-like behavior,and lung injury in mice by inhibiting microglial activation,reducing inflammatory cytokines,and increasing neurons.关键词
六味地黄苷糖/SARS-CoV-2刺突蛋白/神经系统损伤/离子钙结合衔接分子1/神经元细胞核/炎症Key words
Liuwei Dihuang(六味地黄)Active Fraction Combination(LW-AFC)/SARS-CoV-2 spike protein/Nervous system injury/IBA-1/NeuN引用本文复制引用
肖文一,李佳佳,王娇,韦冬晖,韩露,王健辉,蒋宁,周文霞..六味地黄苷糖对SARS-CoV-2刺突蛋白所致神经损伤的保护作用[J].中药药理与临床,2025,41(1):22-28,7.基金项目
国家重点研发计划项目(编号:2022YFC3500304) （编号:2022YFC3500304）
省部共建组分中药国家重点实验室开放课题(编号:CBCM2023101). （编号:CBCM2023101）
