中医药学报2025，Vol.53Issue(5)：9-17,9.DOI:10.19664/j.cnki.1002-2392.250089
海藻甘草反药组合对甲状腺肿大模型大鼠毒性表征及肝脏蛋白合成功能的影响
Toxicological Characterization of the Seaweed-Glycyrrhiza Reverse Drug Combination on the Thyroid Goiter Model Rats and Its Effect on Hepatic Protein Synthesis Function
摘要
Abstract
Objective:To explore whether the seaweed-glycyrrhiza reverse drug combination causes hepatic toxicity and exhibits"opposite"effects on thyroid goiter model rats under different dosage conditions,and to investigate its impact on the hepatic protein synthesis function and related mechanisms.Methods:Ninety male Wistar rats were randomly divided into six groups:control group,model group,positive drug(Euthyrox)group(20 μg·kg-1),low-dose(1.98 g·kg-1),medium-dose(3.96 g·kg-1),and high-dose seaweed-glycyrrhiza(HG-G)group(7.92 g·kg-1),with 15 rats per group.The control group was treated with deionized water by gavage.The other groups were treated with propylthiouracil(PTU)to replicate the thyroid goiter model.After successful model induction,the positive drug group was treated with Euthyrox for 14 days,while the seaweed-glycyrrhiza groups were treated with the respective doses of seaweed-glycyrrhiza solution for 14 days.After the last administration,rats were sacrificed 12 hours later.Serum levels of AST,ALT,ALP,total protein(TP),and albumin(ALB)were measured.Histopathological changes in the liver were observed using hematoxylin-eosin(HE)and Masson staining.mRNA expression of protein kinase B(Akt),mammalian target of rapamycin(mTOR),eukaryotic translation initiation factor 4E binding protein 1(4EBP1),and eukaryotic translation initiation factor 4E(eIF4E)in liver tissue was measured by quantitative real-time PCR(qPCR).The protein expression levels of AKT,mTOR,p-mTOR,and 4EBP1 were detected by Western blotting.Results:Compared with the control group,the model group showed significantly increased ALT levels(P<0.05),and decreased ALB,AST/ALT ratios(P<0.05,P<0.01).The mRNA expressions of AKT,mTOR,4EBP1,and eIF4E were significantly reduced(P<0.05,P<0.01),and the protein expressions of AKT,mTOR,p-mTOR,and 4EBP1 were significantly decreased(P<0.01).Compared with the model group,the HG-D group showed significantly increased levels of TP and ALB(P<0.05,P<0.01),with significantly increased mRNA expression of AKT,mTOR,4EBP1,and eIF4E(P<0.05,P<0.01),and significantly increased protein expression of AKT,mTOR,p-mTOR,and 4EBP1(P<0.01).Compared with the HG-D group,the HG-Z and HG-G groups showed significantly lower p-mTOR levels(P<0.05).Conclusion:The seaweed-glycyrrhiza reverse drug combination did not exhibit obvious toxicity or"opposite"effects on the liver in the thyroid goiter model rats.Instead,it provided varying degrees of protection to hepatic protein synthesis function.The HG-D group showed the best protective effect,superior to the HG-Z and HG-G groups.The mechanism may be related to the activation of the AKT/mTOR/4EBP1 signaling pathway.关键词
海藻/甘草/甲状腺肿大/肝脏蛋白合成/AKT/mTOR/4EBP1Key words
Seaweed/Glycyrrhiza/Thyroid Goiter/Hepatic protein synthesis/AKT/mTOR/4EBP1分类
医药卫生引用本文复制引用
徐向楠,修琳琳,陈绍红,柳海艳,钟赣生,吴美晶,董肖,田颐,廖文勇,刘晓庆,曹灿,于雪,范盎然..海藻甘草反药组合对甲状腺肿大模型大鼠毒性表征及肝脏蛋白合成功能的影响[J].中医药学报,2025,53(5):9-17,9.基金项目
国家自然科学基金项目(81973496) （81973496）
北京中医药大学纵向科研发展基金项目(2024-ZXFZJJ-JW-056) （2024-ZXFZJJ-JW-056）
