基于网络药理学和动物验证探究健脾益肾方对大鼠肾性贫血的影响及机制  

Exploration of the effect and mechanism of Jianpi Yishen formula on renal anemia in rats based on the network pharmacology and animal validation

作　　者：李常慧 赖珍沁 陈秋谷 王蕤 张尚斌[1,2] 李顺民[1] 刘志承[1] 陈剑平[1,2] LI Changhui;LAI Zhenqin;CHEN Qiugu;WANG Rui;ZHANG Shangbin;LI Shunmin;LIU Zhicheng;CHEN Jianping(The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine,Shenzhen 518033,Guangdong Province,China;Shenzhen Traditional Chinese Medicine Hospital,Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation,Shenzhen 518033,Guangdong Province,China)

机构地区：[1]广州中医药大学第四临床医学院,广东深圳518033 [2]深圳市中医院/深圳市医院中药制剂研究重点实验室,广东深圳518033

出　　处：《药学前沿》2025年第2期192-200,共9页China Pharmacist

基　　金：国家自然科学基金青年科学基金项目(81804052);深圳市医疗卫生三名工程项目(SZZYSM202111002);深圳市科技计划项目(JCYJ20240813152222028、ZDSYS201606081515458)。

摘　　要：目的基于高效液相色谱-三重四极杆串联质谱(HPLC-QQQ-MS/MS)、网络药理学、分子对接及实验验证研究健脾益肾方治疗肾性贫血的作用机制。方法采用HPLC-QQQ-MS/MS技术,测定健脾益肾方的化学成分,运用TCMIP v2.0等数据库预测健脾益肾方化学成分与肾性贫血的靶点、通路,绘制出“交集成分-交集靶点-通路”网络图,筛选出健脾益肾方治疗肾性贫血的核心靶点及核心成分,并通过分子对接和动物实验进一步验证核心靶点和成分。结果从健脾益肾方中共鉴定出11个化学成分,通过Draw Venn Diagram平台筛选得到81个交集靶点,提示丝氨酸/苏氨酸蛋白激酶1(AKT1)、磷脂酰肌醇-3-激酶催化亚单位α(PIK3CA)、表皮生长因子受体(EGFR)、B细胞淋巴瘤/白血病-2(BCL2)、V-Ha-Ras肉瘤病毒癌基因同源物(HRAS)等为核心靶点,丹酚酸A、迷迭香酸、大黄酸、毛蕊异黄酮葡萄糖苷和毛蕊异黄酮为核心成分。分子对接结果显示,网络药理学预测的核心靶点和成分可靠性较高;动物实验表明,健脾益肾方显著改善慢性肾脏病大鼠肾损伤和血常规参数,通过抑制EGFR从而治疗肾性贫血。结论通过成分测定和网络药理学关联分析、分子对接及实验验证,阐明健脾益肾方通过抑制EGFR治疗肾性贫血的作用机制,为其临床应用提供参考依据。Objective To study the mechanism of Jianpi Yishen formula in the treatment of renal anemia based on HPLC-QQQ-MS/MS,network pharmacology,molecular docking and experimental verification.Methods The chemical constituents of Jianpi Yishen formula were analyzed by HPLC-QQQ-MS/MS.TCMIP v2.0 and other databases were used to predict the targets and pathways of chemical constituents and renal anemia,and the"intersection component-intersection target-pathway"connection network was drawn to predict the core targets and compounds in the treatment of renal anemia.The core targets and compounds were further validated by molecular docking and animal experiments.Results A total of 11 components were identified from Jianpi Yishen formula.Through Draw Venn Diagram,81 targets in Jianpi Yishen formula related to renal anemia were screened,suggesting that AKT1、PIK3CA、EGFR、BCL2、HRAS,etc may be key targets and Salvianolic acid A,Rosmarinic acid,Rhein,Calycosin-7-glucoside and Calycosin may be key components.Molecular docking results showed that the core targets and components of network pharmacology prediction was of high reliability.Animal experiments showed that Jianpi Yishen formula significantly improved kidney injury and hematological parameters in chronic kidney disease rats and inhibited EGFR to treat renal anemia.Conclusion Through constituents characterization and network pharmacological association analysis,molecular docking and experimental verification,the mechanism of Jianpi Yishen formula in the treatment of renal anemia by inhibiting EGFR was clarified,which can provide a basis for its clinical application.

关 键 词：健脾益肾方 肾性贫血 表皮生长因子受体 网络药理学 高效液相色谱-三重四极杆串联质谱 慢性肾脏病 

分 类 号：R969[医药卫生—药理学]