中华中医药学刊

基于PI3K/AKT/NF-κB通路探究加味泽泻汤对高脂饲喂大鼠血管内皮保护作用机制

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赫雨薇 ¹ , 刘迪 ¹ , 官蜀钧 ¹ , 宫铭 ² , 吴文龙 ¹ , 李婷 ¹ , 张艳 ³ , 赵昕 ²

中华中医药学刊 | 国家项目点击 2026,44(3): 120-128

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中华中医药学刊 |国家项目点击 2026 , 44 (3) : 120 -128

基于PI3K/AKT/NF-κB通路探究加味泽泻汤对高脂饲喂大鼠血管内皮保护作用机制

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赫雨薇¹, 刘迪¹, 官蜀钧¹, 宫铭², 吴文龙¹, 李婷¹, 张艳³, 赵昕²

作者信息

^1.辽宁中医药大学辽宁沈阳 110847

^2.大连医科大学附属第二医院，辽宁大连 116023

^3.辽宁中医药大学附属医院，辽宁沈阳 110032

通讯作者:

赵昕（1970 -），女，浙江绍兴人，主任医师，博士研究生导师，博士后，研究方向：冠心病中西医药物联合介入治疗。E-mail：zx81830@163.com。

张艳（1960 -），女，辽宁丹东人，主任医师、教授，博士研究生导师，博士，研究方向：中西医结合心血管。E-mail：yanzhang1016@126.com。

作者简介:

赫雨薇（1991 -），女（满族），辽宁沈阳人，主治中医师，博士，研究方向：冠心病中西医药物联合介入治疗。

Exploration of Protective Mechanism of Jiawei Zexie Decoction（加味泽泻汤）on Vascular Endothelium in High-Fat Diet-Fed Rats Based on PI3K/AKT/NF-κB Pathway

Yuwei HE¹, Di LIU¹, Shujun GUAN¹, Ming GONG², Wenlong WU¹, Ting LI¹, Yan ZHANG³, Xin ZHAO²

Affiliations

^1.Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning, China

^2.The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning, China

^3.Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning, China

出版时间: 2026-03-10 doi: 10.13193/j.issn.1673-7717.2026.03.023

文章导航

摘要

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目的

探讨加味泽泻汤通过磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/核因子κB（NF-κB）通路对高脂血症内皮损伤的保护作用及潜在机制探析。

方法

将30只SD雄性大鼠（4周龄）随机分为正常组6只，造模组24只，其中造模组24只通过饲喂高脂饮食20周后构建高脂血症模型。将造模成功的24只大鼠随机分为4组，模型组、加味泽泻汤正常剂量组、高剂量组及西药阿托伐他汀钙组。经过4周用药干预后，通过检测大鼠体质量、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）等血脂四项、内皮缩血管肽-1（ET-1）及一氧化氮（NO）等内皮功能相关指标及苏木素-伊红（HE）染色对主动脉组织进行染色后，评价加味泽泻汤治疗高脂血症内皮损伤的治疗效果。随后利用网络药理学分析进一步探究发挥作用的药效机制，通过TCMSP、Swiss Target Prediction、HERB、ETCM和BATMAN数据库预测了中药活性成分及靶点；从GeneCards、OMIM、DisGeNET、TTD数据库中获取了与高脂血症和内皮功能障碍相关的靶点。通过韦恩图及蛋白质-蛋白质相互作用（PPI）网络和富集分析寻找机制通路，并采用实时荧光定量PCR（RT-qPCR）法检测各组大鼠PI3K、AKT1、NF-κB、IL-6、TNF mRNA表达及Western blot法检测内皮损伤通路相关蛋白p-PI3K、PI3K、p-AKT、AKT、NF-κB的表达水平。

结果

与正常组比较，模型组大鼠TC、TG、LDL-C、ET-1水平升高（P < 0.01），HDL-C、NO水平降低（P < 0.05，P < 0.01）。网络药理学分析结果获得加味泽泻汤的活性成分包括24-乙酰泽泻醇A、山柰酚、泽泻醇A、泽泻醇B、泽泻醇C、白术内酯I等29个；PPI网络及拓扑分析后共得到IL-6、AKT1、TNF、IL-1B、STAT3等62个核心靶点，富集通路主要涉及PI3K/AKT信号通路、脂质与动脉粥样硬化、HIF-1信号通路、TNF信号通路等156条信号通路。动物实验验证结果显示，与模型组比较，加味泽泻汤可上调PI3K、AKT1、NF-κB、IL-6、TNF等mRNA表达水平，及p-PI3K、PI3K、p-AKT、AKT、NF-κB蛋白表达（P < 0.01）。

结论

加味泽泻汤具有良好地降低血脂、抑制炎症因子的表达，保护血管内皮功能的作用，其机制可能是通过激活PI3K/AKT/NF-κB信号通路实现的。

关键词

加味泽泻汤 / 高脂血症 / 内皮功能障碍 / 网络药理学 / PI3K/AKT/NFκB通路

Abstract

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Objective

To explore the protective effect and underlying mechanisms of Jiawei Zexie Decoction（加味泽泻汤, JWZXD）on endothelial injury in hyperlipidemia through the phosphatidylinositol-3-kinase/protein kinase B/nuclear factor-κB（PI3K/AKT/NF-κB）pathway.

Methods

Thirty 4-week-old male SD rats were randomly divided into a normal group（n = 6）and a modeling group（n = 24）. The modeling group was fed a high-fat diet for 20 weeks to establish a hyperlipidemia model. The 24 successfully modeled rats were then randomly divided into four groups：the model group, the JWZXD standard dose group, the JWZXD high-dose group, and the atorvastatin calcium group. After 4 weeks of drug intervention, the body weight, four blood lipid parameters［total cholesterol（TC）, triglyceride（TG）, high-density lipoprotein cholesterol（HDL-C）, low-density lipoprotein cholesterol（LDL-C）］and endothelial function-related indicators［endothelin-1（ET-1）, nitric oxide（NO）］were detected, and the aortic tissue was stained with hematoxylin and eosin（HE）to evaluate the therapeutic effect of JWZXD on endothelial injury in hyperlipidemia. Subsequently, the network pharmacology analysis was conducted to further explore the pharmacological mechanisms at play. The active components and targets of JWZXD were predicted using the TCMSP, Swiss Target Prediction, HERB, ETCM and BATMAN databases. The targets related to hyperlipidemia and endothelial dysfunction were retrieved from the GeneCards, OMIM, DisGeNET and TTD databases. Venn diagrams, protein-protein interaction（PPI）networks and enrichment analysis were employed to identify mechanism pathways. Real-time fluorescent quantitative PCR（RT-qPCR）was used to detect the mRNA expressions of PI3K, AKT1, NF-κB, IL-6 and TNF in each group and Western blot analysis was conducted to measure the expression levels of endothelial injury pathway-related proteins p-PI3K, PI3K, p-AKT, AKT and NF-κB.

Results

Compared with the normal group, the model group showed increased levels of TC, TG, LDL-C and ET-1（P < 0.01）, and decreased levels of HDL-C and NO（P < 0.05, P < 0.01）. Network pharmacology analysis identified 29 active ingredients in JWZXD, including 24-acetyl alismol A, kaempferol, alismol A, alismol B, alismol C and atractylenolide I. After PPI network and topological analysis, 62 core targets such as IL-6, AKT1, TNF, IL-1B and STAT3 were identified. Enrichment analysis using the DAVID platform mainly identified 156 signaling pathways, including the PI3K-AKT signaling pathway, lipids and atherosclerosis, HIF-1 signaling pathway, TNF signaling pathway and EGFR tyrosine kinase inhibitor resistance. Animal experiment results showed that compared with the model group, JWZXD down-regulated the mRNA expression levels of PI3K, AKT1, NF-κB, IL-6, TNF, etc., and up-regulated the protein expression levels of endothelial p-PI3K, PI3K, p-AKT and AKT（P < 0.05, P < 0.01）while down-regulated the protein expression of NF-κB（P < 0.05, P < 0.01）.

Conclusion

JWZXD has a good effect on lowering blood lipids, inhibiting the expression of inflammatory factors and protecting vascular endothelial function. Its mechanism may be achieved through the activation of the PI3K/AKT/NF-κB signaling pathway.

Key words

Jiawei Zexie Decoction（加味泽泻汤） / hyperlipidemia / endothelial dysfunction / network pharmacology / PI3K/AKT/NFκB pathway

引用本文

赫雨薇, 刘迪, 官蜀钧, 宫铭, 吴文龙, 李婷, 张艳, 赵昕. 基于PI3K/AKT/NF-κB通路探究加味泽泻汤对高脂饲喂大鼠血管内皮保护作用机制. 中华中医药学刊, 2026 , 44 (3) : 120 -128 . DOI: 10.13193/j.issn.1673-7717.2026.03.023

Yuwei HE, Di LIU, Shujun GUAN, Ming GONG, Wenlong WU, Ting LI, Yan ZHANG, Xin ZHAO. Exploration of Protective Mechanism of Jiawei Zexie Decoction（加味泽泻汤）on Vascular Endothelium in High-Fat Diet-Fed Rats Based on PI3K/AKT/NF-κB Pathway[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (3) : 120 -128 . DOI: 10.13193/j.issn.1673-7717.2026.03.023

基金

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国家自然科学基金面上项目(82370438)
大连医科大学交叉科研合作课题组项目(JCHZ2023014)

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2026年第44卷第3期

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doi: 10.13193/j.issn.1673-7717.2026.03.023

首发时间：2026-10-14
出版时间：2026-03-10

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基金

国家自然科学基金面上项目(82370438)

大连医科大学交叉科研合作课题组项目(JCHZ2023014)

作者信息

^1.辽宁中医药大学辽宁沈阳 110847

^2.大连医科大学附属第二医院，辽宁大连 116023

^3.辽宁中医药大学附属医院，辽宁沈阳 110032

通讯作者:

赵昕（1970 -），女，浙江绍兴人，主任医师，博士研究生导师，博士后，研究方向：冠心病中西医药物联合介入治疗。E-mail：zx81830@163.com。

张艳（1960 -），女，辽宁丹东人，主任医师、教授，博士研究生导师，博士，研究方向：中西医结合心血管。E-mail：yanzhang1016@126.com。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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