中国药理学通报2025，Vol.41Issue(5)：843-850,8.DOI:10.12360/CPB202408073
补骨脂素对正常大鼠和阴虚大鼠肝脏毒性差异研究及机制初探
Difference in liver toxicity between normal rats and Yin deficiency rats treated with psoralen and preliminary exploration of its mechanism
摘要
Abstract
Aim To study the difference in hepatotox-icity of psoralen on normal rats and Yin-deficiency rats from the perspective of lipid metabolism,so as to help explain the mechanism of psoralen cautiously used in patients with Yin deficiency recorded in ancient books.Methods SD rats were randomly divided into the nor-mal control group(carboxymethyl cellulose-Na,CMC-Na),normal administration group(CMC-Na+psor-alen),Yin-deficiency control group(CMC-Na+thy-roxine)and Yin-deficiency administration group(CMC-Na+thyroxine+psoralen).The model of Yin-deficiency was established by thyroxine(1 mg·kg-1)for ten days,and then psoralen(200 mg·kg-1)was given for three days.The serum indexes related to liver injury were detected by automatic biochemical analy-zer,the morphological changes of liver tissue were ob-served using HE and oil red O staining,and the relative transcription levels of lipid metabolism related enzymes and mRNA of transporter and endoplasmic reticulum stress related factors were detected using Real-time PCR.Results After intragastric administration of psoralen for three days,compared with the normal group,the levels of serum alanine aminotransferase(ALT),aspartate transaminase(AST),total bile acid(TBA)and triglyeride(TG)in Yin deficiency group increased more significantly,while TC,ALB and TP de-creased more significantly,and liver HE and oil red O staining showed more obvious lipid degeneration.TG synthesis factors adrenocortical carcinoma(ACC),fatty acid synthase(FASN)and sterolregulatory element binding protein-1(SREBP-1)were down-regulated more significantly,TG transport factors mili-total pro-tein(MTP)and lipoprotein pipase(LPL)were down-regulated more evidently,fatty acid β-oxidation related factors carnitine palmitoyltransferase 1A(CPT1A),carnitine/organic cation transporter 2(OCTN2)and peroxisome proliferators-activated receptors-alpha(PPARα)were down-regulated more apparently,TC transporter adenosine triphosphate binding cassette transporter G8(ABCG8)and bile acid receptor farne-soid X receptor(FXR)were down-regulated more ob-viously,and endoplasmic reticulum stress factor activa-ting transcription factor 4(ATF4)was up-regulated more significantly.Conclusions Psoralen can cause more severe hepatotoxicity in Yin deficiency rats than that in normal administration group,and its mechanism may be related to the disorder of hepatic lipid metabo-lism,aggravation of hepatic cholestasis and steatosis,and activation of endoplasmic reticulum stress re-sponse.关键词
补骨脂素/阴虚/大鼠/肝毒性/脂质代谢/内质网应激Key words
psoralen/Yin deficiency/rats/hepatotox-icity/lipid metabolism/endoplasmic reticulum stress引用本文复制引用
裴天仙,李福珍,陈梦颖,王学童,邱丽珍,袭恒豫,周昆..补骨脂素对正常大鼠和阴虚大鼠肝脏毒性差异研究及机制初探[J].中国药理学通报,2025,41(5):843-850,8.基金项目
国家自然科学基金资助项目(No 81673826) （No 81673826）
组分中药国家重点实验室资助课题(No CBCM2023203) （No CBCM2023203）
天津中医药大学"雏鹰计划"项目(No XJS2023212 （）
XJS2024211) （）
天津市教委科研计划项目(No 2023KJ135) （No 2023KJ135）
