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

作　　者：肖文一 李佳佳 王娇 韦冬晖 韩露 王健辉 蒋宁 周文霞 XIAO Wenyi;LI Jiaja;WANG Jiao;WEI Donghui;HAN Lu;ANG Jjanhui;JIANG Ning;ZHOU Wenxia(Graduate School of Nanjing University of Chinese Medicine,Nanjing 210023;National Key Laboratory of National Security Drugs for Special Needs,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850)

机构地区：[1]南京中医药大学研究生学院,南京210023 [2]军事科学院军事医学研究院,国家安全特需药品全国重点实验室,北京100850

出　　处：《中药药理与临床》2025年第1期22-28,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家重点研发计划项目(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)。

摘　　要：目的:研究六味地黄苷糖对新型冠状病毒(SARS-CoV-2)刺突蛋白所致神经系统损伤改善作用和潜在作用途径。方法:将34只C57/6J小鼠依体质量和自主活动性分为正常对照组、模型对照组和六味地黄苷糖1.6 g/kg组。给药组灌胃相应药物,模型对照组及正常对照组灌胃给予等体积去离子水。预防给药7 d后,造模小鼠单次尾静脉注射刺突蛋白造模,正常对照组注射等体积生理盐水。继续灌胃给药28 d,共计35 d后采用转棒实验检测小鼠运动能力;旷场和埋珠实验检测小鼠焦虑样行为;悬尾实验检测小鼠抑郁样行为;新物体识别实验检测小鼠学习记忆能力;HE染色检测小鼠肺组织病理损伤;ELISA法检测海马组织中白细胞介素-6(IL-6)和肿瘤坏死因子α(TNF-α)含量;免疫荧光法检测小鼠海马离子钙结合衔接分子1(IBA-1)和神经元细胞核(NeuN)的荧光阳性细胞数目。结果:与正常对照组比较,模型对照组小鼠在棒时间显著降低(P<0.01),掩埋珠子个数显著增加(P<0.01),进入中心区次数显著降低(P<0.05),肺组织损伤评分显著增加(P<0.01),海马组织Iba-1阳性细胞数显著增加(P<0.01),NeuN阳性细胞数明显减少(P<0.05),海马组织中IL-6和TNF-α含量显著增加(P<0.01);与模型对照组比较,六味地黄苷糖1.6 g/kg组小鼠在棒时间明显提高(P<0.05),掩埋珠子个数明显降低(P<0.05),肺组织损伤评分明显降低(P<0.05),海马组织IBA-1阳性细胞数明显减少(P<0.05),NeuN阳性细胞数明显增多(P<0.05),海马组织中IL-6和TNF-α含量明显降低(P<0.05)。结论:六味地黄苷糖对刺突蛋白导致的小鼠运动能力降低、焦虑样行为、肺损伤有一定防治作用,可能是通过抑制小胶质细胞激活、降低炎症因子,增加神经元数量。Objective:To study the effects and potential pathways of Liuwei Dihuang(六味地黄)Active Fraction Combination(LW-AFC)in ameliorating nervous system damage caused by the spike protein of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods: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 behavior.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 calcium-binding adaptor molecule 1(Iba-1)and neuronal nuclei(NeuN)in the hippocampus.Hematoxylin-eosin staining was performed to assess the pathological damage in the lung tissue.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of interleukin-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 decrease 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

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 

分 类 号：R285.5[医药卫生—中药学]