复方人参对机体缺氧损伤的保护作用及其分子机制研究  

Study on the protective effect of compound ginseng on hypoxic injury and its molecular mechanism

作　　者：陈卉 郭衬衬 潘雅琪 边爽 吉文鑫 龙超良 石永平 汪海 CHEN Hui;GOU Chen-chen;PAN Ya-qi;BIAN Shuang;JI Wen-xin;LONG Chao-liang;SHI Yong-ping;WANG Hai(School of Health Science,Jiangsu Normal University;Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells,Xuzhou 221116,China;Thadweik Academy of Medicine,Beijing 100039,China;School of Life Science,Jiangsu Normal University,Xuzhou 221116,China)

机构地区：[1]江苏师范大学健康科学学院 [2]江苏省内皮细胞靶向性心血管药物创制工程研究中心,徐州221116 [3]北京赛德维康医药研究院,北京100039 [4]江苏师范大学生命科学学院,徐州221116

出　　处：《天然产物研究与开发》2025年第1期27-39,共13页Natural Product Research and Development

基　　金：江苏省研究生科研与实践创新计划(KYCX23-2908)。

摘　　要：探究复方人参(compound ginseng,CGS)的抗缺氧作用及其分子机制。构建小鼠密闭缺氧模型、亚硝酸钠中毒模型、急性脑缺血模型以及全心缺血缺氧模型,观察CGS对小鼠的存活时间、喘气时间、喘气次数、丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)活力、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性、乳酸脱氢酶(lactic dehydrogenase,LDH)活力和肌酸激酶(creatine kinase,CK)活力。利用网络药理学预测CGS的抗缺氧相关机制,并采用分子对接方法验证网络药理学筛选所得CGS活性成分与机体靶点之间的亲和性,检测小鼠体内缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA表达量。结果显示,CGS可以显著延长密闭缺氧实验、亚硝酸钠中毒实验和全心缺血缺氧实验小鼠的存活时间以及急性脑缺血实验的喘气时间和喘气次数;CGS能够降低小鼠血清中的MDA含量、LDH和CK活力,提升SOD、GSH-Px活性。采用网络药理学预测出226条CGS抗缺氧通路,其中关键通路有HIF-1α通路;密闭缺氧实验结果证实CGS可以显著提升HIF-1α表达,下调VEGF表达。综上,CGS具有耐缺氧作用,其作用可能与激活HIF-1α/VEGF通路,提高血液携氧能力和氧利用率,增强抗氧化活性有关。This study aims to investigate the anti-hypoxic effect of compound ginseng(CGS)and its molecular mechanism.The atmospheric pressure hypoxia tolerance model,the sodium nitrite poisoning model,the acute cerebral ischemia model and the whole heart ischemia-hypoxia model were constructed,and the effects of CGS on survival time,gasping time,gasping frequency,malondialdehyde(MDA)content,superoxide dismutase(SOD)activity,glutathione peroxidase(GSH-Px)activity,lactic dehydrogenase(LDH)activity,and creatine kinase(CK)activity were oberved.Network pharmacology was utilized to predict the anti-hypoxia related mechanism of CGS,and molecular docking method was used to verify the affinity between the active ingredients of CGS and the body targets obtained from network pharmacology screening,and to detect the mRNA expression of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)in mice.The results showed that CGS significantly prolonged the survival time of mice in the atmospheric pressure hypoxia tolerance experiment,sodium nitrite intoxication experiment and whole heart ischemia-hypoxia experiment,as well as gasping time and gasping frequency in the acute cerebral ischemia experiment;CGS was able to reduce the serum levels of MDA,LDH,and CK viability,and elevate the activities of SOD and GSH-Px in mice.Network pharmacology was used to predict 226 anti-hypoxia pathways of CGS,among which the key pathway was the HIF-1α pathway.the results of the confined hypoxia experiments confirmed that CGS could significantly elevate the expression of HIF-1α and down-regulate the expression of VEGF.In conclusion,CGS has the anti-hypoxia effect,and its action may be related to the activation of the HIF-1α/VEGF pathway,which improves the oxygen-carrying capacity of the blood and oxygen utilization,and enhances the antioxidant activity.

关 键 词：复方人参 抗缺氧 缺血性缺氧 氧化应激 

分 类 号：R284.2[医药卫生—中药学]