Page 27 - 《中国药房》2024年3期

·药学研究·

蓝盆花醇提物抗肝纤维化的作用及机制研究
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金 蓉 ，赵晓璐，颜羽昕，高晓阳，张春艳，李明奇，马月宏（内蒙古医科大学基础医学院，呼和浩特 010110）
中图分类号 R965；R285 文献标志码 A 文章编号 1001-0408（2024）03-0277-06
DOI 10.6039/j.issn.1001-0408.2024.03.03

摘 要 目的 探讨蓝盆花醇提物抗肝纤维化（HF）的作用及机制。方法 采用四氯化碳灌胃法建立HF模型。通过观察肝组织病
理学变化，检测HF指标[α-平滑肌肌动蛋白（α-SMA）、胶原蛋白Ⅰ（Collagen Ⅰ）]及磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信
号通路相关因子mRNA和蛋白表达水平，考察低、中、高剂量（50、100、200 mg/kg）蓝盆花醇提物对HF模型大鼠的改善作用及可能
机制。按1 800 mg/（kg·d）（以生药量计）灌胃大鼠蓝盆花醇提物制备含药血清，以低、中、高浓度（将含药血清稀释至10%、15%、
20%）蓝盆花醇提物含药血清干预HSC-T6细胞，观察其对微小RNA-21（miRNA-21）表达的影响；将miRNA-21模拟物/抑制剂转染
至HSC-T6细胞，并检测PI3K/Akt信号通路相关因子的mRNA和蛋白表达水平。结果 体内实验结果表明，低、中、高剂量蓝盆花
醇提物均可显著改善HF模型大鼠肝组织病理学变化，降低其胶原百分比（P＜0.01），下调其HF指标及PI3K、Akt的mRNA和蛋白
表达（P＜0.01），上调其磷酸酶及张力蛋白同源基因（PTEN）的mRNA及其蛋白表达（P＜0.01）。体外实验结果表明，低、中、高浓
度蓝盆花醇提物含药血清均可显著抑制miRNA-21的表达（P＜0.01）；转染miRNA-21模拟物后，细胞中PI3K、Akt的mRNA和蛋
白表达上调（P＜0.01），PTEN的mRNA及其蛋白表达下调（P＜0.01）；而转染miRNA-21抑制剂后，细胞中上述指标的变化与转染
miRNA-21 模拟物相反（P＜0.01）。结论 蓝盆花醇提物可通过抑制 miRNA-21 表达、上调 PTEN 表达，进而抑制 PI3K/Akt 信号通
路活性，最终发挥抗HF的作用。
关键词 蓝盆花醇提物；肝纤维化；磷脂酰肌醇3激酶/蛋白激酶B信号通路；磷酸酶及张力蛋白同源基因；微小RNA-21

Study on the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis
JIN Rong，ZHAO Xiaolu，YAN Yuxin，GAO Xiaoyang，ZHANG Chunyan，LI Mingqi，MA Yuehong（School of
Basic Medical Sciences， Inner Mongolia Medical University， Hohhot 010110， China）

ABSTRACT OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic
fibrosis （HF）. METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the
pathological changes in liver tissue， mRNA and protein expressions of HF indexes [α-smooth muscle actin （α-SMA）， collagen type
Ⅰ] and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway-related factors were detected， and the improvement
effects and possible mechanism of low-dose， medium-dose and high-dose （50， 100， 200 mg/kg） of alcoholic extract from S.
comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic
extract from S. comosa at a concentration of 1 800 mg/（kg·d） （calculated by the amount of raw material）. The effects of drug-
containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of
HSC-T6 cells with low， medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa （diluted to
10%， 15%， 20%）. miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells， and the mRNA and protein expressions of
factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low，
medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of
HF rats， and the percentage of collagen was significantly reduced （P＜0.01）； mRNA and protein expressions of the indicators
related to HF as well as PI3K and Akt were significantly reduced （P＜0.01）， and mRNA and protein expressions of phosphatase
and tensin homolog deleted on chromosome ten （PTEN） were
Δ 基金项目 国家自然科学基金项目（No.81960759）；内蒙古自治 increased in liver tissue of rats （P＜0.01）. The results of in
区自然科学基金项目（No.2019MS08010）；内蒙古自治区人才开发基 vitro experiments showed that drug-containing serum of
金项目（No.22056）；内蒙古医科大学重点项目（No.YKD2022ZD019）；
alcoholic extract from S. comosa significantly inhibited the
内蒙古医科大学蒙药抗肝纤维化作用研究科技创新团队项目（No.
expression of miRNA-21 at low， medium and high
YKD2022TD039） concentrations （P＜0.01）； whereas after transfection with
＊第一作者 讲师，硕士。研究方向：中蒙药的肝纤维化药理。
E-mail：623633856@qq.com miRNA-21 mimics， it was found that miRNA-21 mimics
# 通信作者 教授，硕士。研究方向：中蒙药的肝纤维化药理。 significantly increased mRNA and protein expressions of PI3K
E-mail：myh19982002@sina.com and Akt （P＜0.01）， while significantly decreased mRNA and

中国药房 2024年第35卷第3期 China Pharmacy 2024 Vol. 35 No. 3 · 277 ·