首页|蓍草防治急性肝损伤的作用机制及量效关系研究

蓍草防治急性肝损伤的作用机制及量效关系研究

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目的 基于网络药理学和多指标综合指数法，探究蓍草防治急性肝损伤的作用机制，并评价不同剂量蓍草(1。56、3。12、6。24、9。36、12。48、15。60 g·kg-1)的肝保护作用。方法 运用网络药理学预测蓍草对肝脏损伤可能的作用靶点和与相关疾病的潜在关系，并通过分子对接和免疫荧光检测进行验证。采用四氯化碳橄榄油溶液诱导大鼠急性肝损伤，测定了多项指标包括肝指数、ALT、AST、TNF-α、IL-6、IL-1β、CAT、SOD、GSH-px、MDA和GSH。最后采用主成分分析和CRITIC权重分析法综合评价蓍草对肝脏保护效应。结果 共获得351个蓍草和急性肝损伤的共同靶点。网络药理学分析发现，AKT1、TNF和ALB为前3个核心靶点，主要涉及PI3K/AKT信号通路。免疫荧光染色显示，蓍草下调了急性肝损伤大鼠肝脏中PI3K、AKT和TNF蛋白的表达，上调了 ALB蛋白的表达。与对照组相比，模型组中各指标差异有统计学意义;与模型组比较，蓍草不同剂量给药组能较好地改善急性肝损伤大鼠的各项指标水平，并呈一定的量效关系。综合主成分分析和多指标综合指数法得出，蓍草在浓度为15。60g·kg-1时的肝保护作用最明显。结论 蓍草具有防治急性肝损伤的作用，这可能与蓍草调节PI3K信号通路有关;当蓍草剂量为15。60g·kg-1 时，其药效最好，这为蓍草的合理应用奠定了基础。
Mechanism and Dosage-effect Relationship of Achillea Alpina L.in Preventing and Treating Acute Liver Injury
OBJECTIVE To investigate the mechanism of Achillea alpina L.in preventing and treating acute liver injury and assess the hepatoprotective effect of different doses of Achillea alpina L.(1.56,3.12,6.24,9.36,12.48,15.60 g·kg-1)using network pharmacology and a multi-index comprehensive index method.METHODS Network pharmacology was used to predict the potential targets of Achillea alpina L.in liver injury and its potential relationship with related diseases.The results were validated using molecular docking and immune fluorescence detection.Acute liver injury was induced in rats using carbon tetrachloride and olive oil solution,and multiple indicators were measured,including liver index,ALT,AST,TNF-α,IL-6,IL-1 β,CAT,SOD,GSH-px,MDA,and GSH.Finally,principal component analysis and CRITIC weight analysis were used to comprehensively evaluate the hepatoprotective effect of Achillea alpina L..RESULTS A total of 351 common targets for Achillea alpina L.and acute liver injury were obtained.Network pharmacology analysis revealed that AKT1,TNF and ALB were the top 3 core targets,mainly involving the PI3K/AKT signaling pathway.Immune fluorescence staining showed that Achillea alpina L.downregulated the expression of PI3K,AKT,and TNF proteins,while upregulating the expression of ALB protein in the liver of rats with acute liver injury.Compared with the control group,the differences in various indicators in the model group were statistically significant.When compared with the model group,Achillea alpina L.at different doses could better improve the levels of various indicators in rats with acute liver injury and exhibited a certain dose-effect relationship.Through principal component analysis and a multi-index comprehensive index method,it was determined that the dosage of 15.60 g·kg-1 of Achillea alpina L.had the most significant hepatoprotective effect.CONCLUSION Achillea alpina L.has a preventive and therapeutic effect on acute liver injury,which may be related to the regulation of the PI3K signaling pathway by Achillea alpina L.When the dosage of Achillea alpina L.is 15.60 g·kg-1,it exhibits the best therapeutic effect,which provides a basis for the rational clinical application of Achillea alpina L..

Achillea alpina L.PI3K/AKT signal pathwayCRITIC weight analysis methodmulti-index comprehensive index methoddose-effect relationship

王超、付瑞嘉、左倩、曾晓涛、徐顶巧、唐于平、刘继平

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陕西中医药大学药学院,陕西咸阳 712046

蓍草 PI3K/AKT信号通路 CRITIC权重分析法 多指标综合指数法 量效关系

国家重点研发计划项目

2019YFC1711003

2024

10.13748/j.cnki.issn1007-7693.20231275

中国现代应用药学
中国药学会

中国现代应用药学

CSTPCD北大核心
影响因子：0.877
ISSN：1007-7693
年,卷(期)：2024.41(15)