中国中医急症2025,Vol.34Issue(7):1132-1137,6.DOI:10.3969/j.issn.1004-745X.2025.07.002
甘露消毒汤调控SARS-CoV-2假病毒感染hACE2小鼠RAS轴失衡的机制研究
Mechanism Study of Ganlu Xiaodu Decoction in Regulating RAS Axis Imbalance in hACE2 Transgenic Mice Infected with SARS-CoV-2 Pseudovirus
摘要
Abstract
Objective:To investigate the effect of Ganlu Xiaodu Decoction on the expression levels of RAS axis-related targets in hACE2 transgenic mice infected with SARS-CoV-2 pseudovirus,and to explore its therapeutic mechanism.Methods:60 K18-hACE2 transgenic mice were randomly divided into 5 groups:normal group,mod-el group,low-dose Ganlu Xiaodu Decoction group,medium-dose Ganlu Xiaodu Decoction group,and high-dose Ganlu Xiaodu Decoction group.Except for the normal group,all other groups were inoculated with SARS-CoV-2 pseudovirus via nasal drops to establish the infection model.After successful modeling,Ganlu Xiaodu Decoction was administered for intervention,and samples were collected on day 7 after intervention.The general conditions,body weight changes,and lung indices were recorded;pathological changes in lung tissues were evaluated.ELISA was used to detect the levels of Ang(1-7),AngⅡ,and eNOS in lung tissues.Immunohistochemistry was employed to measure the expression of ACE2 and AT1R proteins.qPCR was performed to analyze the mRNA expression of ACE2,ACE,MAS,and AT1R.Western blotting was used to determine the protein levels of ACE2,ACE,MAS,and AT1R.Results:Compared with the normal group,the model group showed deteriorated general condition,signifi-cantly decreased body weight gain,increased lung index and pulmonary pathology scores,elevated levels of AngⅡand AT1R mRNA and protein expression in lung tissue(P<0.05),and reduced levels of Ang(1-7)and eNOS as well as decreased ACE2 and MAS mRNA and protein expression(P<0.05).There was no significant change in ACE mRNA or protein expression(P>0.05).Compared with the model group,Ganlu Xiaodu Decoction treatment improved the general condition of mice,increased body weight gain,reduced lung index and pulmonary pathology scores,decreased levels of AngⅡ and AT1R mRNA and protein expression(P<0.05),and increased levels of Ang(1-7)and eNOS along with upregulated ACE2 and MAS mRNA and protein expression(P<0.05).No significant changes were observed in ACE mRNA or protein expression(P>0.05).Overall,the high-dose Ganlu Xiaodu De-coction group showed the most significant effects.Conclusion:Ganlu Xiaodu Decoction may exert anti-inflammato-ry effects and improve endothelial injury by modulating the expression of key components in the Ang(1-7)/MAS axis and the AngⅡ/ATIR axis in hACE2 transgenic mice infected with SARS-CoV-2 pseudovirus,thereby restor-ing RAS homeostasis.关键词
严重急性呼吸综合征冠状病毒2型/甘露消毒汤/hACE2/ACE2/Ang(1-7)/MAS/ACE/AngⅡ/AT1R/小鼠Key words
SARS-CoV-2 pseudovirus/Ganlu Xiaodu Decoction/hACE2/ACE2/Ang(1-7)/Mas/ACE/AngⅡ/AT1R/Mice分类
医药卫生引用本文复制引用
武美彤,于雪洁,吴振起,张天宇,李美琪,张希宁,杨馥语,赵炟,李骄昌,齐兆东..甘露消毒汤调控SARS-CoV-2假病毒感染hACE2小鼠RAS轴失衡的机制研究[J].中国中医急症,2025,34(7):1132-1137,6.基金项目
国家自然科学基金面上项目(82074494) (82074494)