| 白海龙,边云,孟晓峰,等.轻盈祛浊汤治疗糖尿病肾病的网络药理学机制分析[J].安徽医药,2025,29(4):671-676. |
| 轻盈祛浊汤治疗糖尿病肾病的网络药理学机制分析 |
| Network pharmacological mechanism of Qingying Quzhuo decoction in the treatment of diabetic nephropathy |
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| DOI：10.3969/j.issn.1009-6469.2025.04.007 |
| 中文关键词: 糖尿病肾病 轻盈祛浊汤 痰湿瘀阻 网络药理学 作用机制 |
| 英文关键词: Diabetic nephropathies Qingying Quzhuo decoction Phlegm-dampness and blood stasis Network pharmacology Mechanism of action |
| 基金项目:河北省中医药管理局科研计划项目( 2020465) |
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| 中文摘要: |
| 目的探讨轻盈祛浊汤治疗糖尿病肾病( DN)的作用机制。方法利用网络药理学预测轻盈祛浊汤治疗 DN的作用机制，并通过分子对接预测活性成分的结合部位。结合网络药理学及分子对接结果，构建 DN大鼠模型， 2023年 1—6月，将 60只大鼠分为正常组、模型组、马来酸依那普利组、轻盈祛浊汤组，每组 15只。治疗 8周后比较四组大鼠 24 h尿微量白蛋白( urinary microalbuminexcretion rate，UAER)、尿素氮、血肌酐水平和钠 /葡萄糖协同转运蛋白 1(recombinant sodium/glucose cotransporter 1，SGLT1)A1腺苷受体( A1 adenosine receptor，A1AR)蛋白表达水平。结果网络药理学共筛选出轻盈祛浊汤有效成分 1 114种，作用靶点，269个， DN相关靶点 2 020个，其交集靶点 174个。基因本体富集( GO)和基因组的京都百科全书( KEGG)分析得出主要涉及信号转导、炎症反应、细胞凋亡等一系列的生物学反应过程，主要参与丝裂原活化蛋白激酶 /核因子 κB(mitogen-ac. tivated protein kinase/nuclear factor kappa-B，pMAPK/NF-κB)、 NOD样受体家族蛋白 3/白细胞介素 -1β(NOD-like receptor protein 3/interleukin-1β，NLRP3/IL-1β)、白细胞介素 6/信号传导和转录激活因子 3(interleukin-6/signal transducer and activator of tran. scription 3，IL-6/STAT3)、肿瘤坏死因子( tumor necrosis factor，TNF)、肿瘤蛋白 p53(tumor protein 53，P53)和前列腺素内过氧化物合酶( prostaglandin-endoperoxide synthase 2，PTGS2)等信号通路的调控。分子对接表明，轻盈祛浊汤主要成分与 DN靶点的结合活性较强。模型组大鼠 24 h UAER［(4 539.71±516.03)μg/24 h比( 226.59±72.71)μg/24 h］、血肌酐［(85.63±12.96)mL·kg.1· min.1比( 0.48±0.12)mL·kg.1 ·min.1］、 SGLT1(1.17±0.07比 0.82±0.06)高于正常组，而模型组大鼠尿素氮、 A1AR低于正常组( P<0.05)。马来酸依那普利片组大鼠 24 h UAER、血肌酐、 SGLT1低于模型组，马来酸依那普利片组大鼠尿素氮、 A1AR高于模型组(P<0.05)。轻盈祛浊汤组大鼠 24 h UAER、血肌酐、 SGLT1低于马来酸依那普利片组，而轻盈祛浊汤组大鼠尿素氮、 A1AR高于马来酸依那普利片组( P<0.05)。结论轻盈祛浊汤可通过调节 pMAPK/NF-κB、NLRP3/IL-1β、IL-6/STAT3、TNF、P53和 PTGS2信号通路发挥治疗 DN的作用。 |
| 英文摘要: |
| Objective To investigate the mechanism of Qingying Quzhuo decoction in the treatment of diabetic nephropathy.Meth. ods Network pharmacology was used to predict the mechanism, and the binding sites of active ingredients were predicted by molecu.lar docking. Combined with the results of network pharmacology and molecular docking, a rat model of diabetic nephropathy was estab.lished. From January to June 2023, 60 rats were randomly assigned into normal group, model group, enalapril maleate group and Qingy. ing Quzhuo decoction group, with 15 rats in each group. After 8 w of treatment, 24 h urinary microalbuminexcretion rate (UAER), ureanitrogen, serum creatinine levels and protein expression levels of recombinant sodium/glucose cotransporter 1 (SGLT1) and A1 adenos.ine receptor (A1AR).Results A total of 1 114 kinds of active constituents of Qingying Quzhuo decoction were selected by networkpharmacology, with 269 targets, 2020 targets related to diabetic nephropathy and 174 intersection targets. GO and KEGG analysis re.sults showed that it mainly involved a series of biological reaction processes such as signal transduction, inflammation and apoptosis,and involved primarily in the regulation of mitogen-activated protein kinase/nuclear factor kappa-B (pMAPK/NF-κB), NOD-like recep. tor protein 3/Interleukin-1β (NLRP3/IL-1β), interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3), tumor necro. sis factor (TNF), tumor protein 53 (P53) and prostaglandin-endoperoxide synthase 2 (PTGS2) signaling pathways. Molecular docking showed that the main constituents of Qingying Quzhuo decoction had strong binding activity to the targets of diabetic nephropathy. Com.pared with normal group, 24 h UAER [(4 539.71±516.03) μg/24 h vs. (226.59±72.71) μg/24 h], serum creatinine [(85.63±12.96) mL· kg.1·min.1 vs. (0.48±0.12) mL·kg.1·min.1] and SGLT1 (1.17±0.07 vs. 0.82±0.06) were increased in model group, while urea nitrogen and A1AR were decreased in model group (P<0.05). Compared with model group, 24 h UAER, serum creatinine and SGLT1 were de.creased in enalapril maleate tablet group, while urea nitrogen and A1AR were increased in enalapril maleate tablet group (P<0.05). Compared with enalapril maleate tablet group, 24 h UAER, serum creatinine and SGLT1 of rats were decreased in Qingying Quzhuo group, and urea nitrogen and A1AR of rats were increased in Qingying Quzhuo group (P<0.05). Conclusion Qingying Quzhuo decoc. tion can play a role in the treatment of diabetic nephropathy by regulating pMAPK/NF-κB, NLRP3/IL-1β, IL-6/STAT3, TNF, P53 and PTGS2 signaling pathways. |
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