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蓝盆花醇提物抗肝纤维化的作用及机制研究

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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。
Study on the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis
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 typeⅠ]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 increased in liver tissue of rats(P＜0.01).The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S.comosa significantly inhibited the expression of miRNA-21 at low,medium and high concentrations(P＜0.01);whereas after transfection with miRNA-21 mimics,it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt(P＜0.01),while significantly decreased mRNA and protein expressions of PTEN(P＜0.01);after transfection with miRNA-21 inhibitor,the changes of above indexes were opposite to the above results(P＜0.01).CONCLUSIONS Alcoholic extracts of S.comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21,so as to achieve the effect of anti-hepatic fibrosis.

alcoholic extract from Scabiosa comosahepatic fibrosisPI3K/Akt signaling pathwayPTENmiRNA-21

金蓉、赵晓璐、颜羽昕、高晓阳、张春艳、李明奇、马月宏

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内蒙古医科大学基础医学院,呼和浩特 010110

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

国家自然科学基金项目内蒙古自治区自然科学基金项目内蒙古自治区人才开发基金项目内蒙古医科大学重点项目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

819607592019MS0801022056YKD2022ZD019YKD2022TD039

2024

10.6039/j.issn.1001-0408.2024.03.03

中国药房
中国医院协会,中国药房杂志社

中国药房

CSTPCD北大核心
影响因子：0.956
ISSN：1001-0408
年,卷(期)：2024.35(3)
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