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淫羊藿苷通过调控HMGB1/TLRs/NF-κB信号通路和炎症反应缓解糖尿病肾病

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中草药 | 药理与临床 2026,57(13): 5130-5139

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中草药 |药理与临床 2026 , 57 (13) : 5130 -5139

淫羊藿苷通过调控HMGB1/TLRs/NF-κB信号通路和炎症反应缓解糖尿病肾病

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徐长青¹, 刘宗梅², 张倩³, 付小燕⁴

作者信息

通讯作者:

付小燕

作者简介:

徐长青: 徐长青（1973—），博士，副教授，副主任医师，研究方向为内分泌代谢疾病中医药防治。E-mail:2272549398@qq.com

Icariin alleviates diabetic kidney disease by regulating HMGB1/TLRs/NF-κB signaling pathway and inflammatory response

XU Changqing, LIU Zongmei, ZHANG Qian, FU Xiaoyan

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doi: 10.7501/j.issn.0253-2670.2026.13.016

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摘要

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目的探讨淫羊藿苷对糖尿病肾病（diabetic kidney disease，DKD）的治疗作用，并从肾脏炎症反应及相关炎症信号通路的角度阐明其分子机制。方法采用C57BL/KsJ db/db小鼠构建DKD模型，以同背景db/m小鼠作为对照组。db/db小鼠随机分为模型组、达格列净（1.6 mg/kg）组及淫羊藿苷高、中、低剂量（120、60、30 mg/kg）组，每组10只。给予药物连续干预4周，检测小鼠体质量、血糖、尿蛋白、血脂、血肌酐等生化指标；通过苏木素-伊红（hematoxylin-eosin，HE）染色、透射电镜观察肾脏病理变化；采用免疫荧光检测肾小球系膜细胞外基质蛋白纤连蛋白（fibronectin，FN）和Ⅳ型胶原（collagen type IV，Col-Ⅳ）表达；通过ELISA和Western blotting检测炎症因子白细胞介素-1β（interleukin-1β，IL-1β）、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）及高迁移率族蛋白B1（high mobility group box 1，HMGB1）/Toll样受体（Toll-like receptors，TLRs）/核因子-κB（nuclear factor-κB，NF-κB）信号通路相关蛋白表达。体外实验以高糖诱导SV40 MES-13细胞，观察淫羊藿苷对细胞外基质蛋白表达的影响。结果体内实验结果显示，高剂量的淫羊藿苷可显著降低DKD小鼠的体质量、尿蛋白、血脂及血肌酐水平（P＜0.01、0.001），减轻肾小球系膜扩张、基底膜增厚及足突融合等病理改变（P＜0.001），降低血浆及肾组织中IL-1β、IL-6和TNF-α水平（P＜0.01、0.001），减少肾脏巨噬细胞浸润，并显著抑制肾组织中HMGB1、TLR2、TLR4及p-p65的蛋白表达（P＜0.001）。体外实验结果显示，淫羊藿苷可抑制高糖诱导的肾小球系膜细胞中FN和Col-Ⅳ的表达。结论淫羊藿苷能有效抑制HMGB1/TLRs/NF-κB信号通路，进而减轻肾脏炎症反应与细胞外基质异常积聚，最终改善DKD的病理损伤。

关键词

糖尿病肾病 / 淫羊藿苷 / 炎症反应 / HMGB1/TLRs/NF-κB信号通路 / 细胞外基质

Abstract

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Objective To investigate the therapeutic effect of icariin on diabetic kidney disease (DKD) and elucidate its molecular mechanism from the perspective of renal inflammatory response and related inflammatory signaling pathways. Methods A DKD model was established using C57BL/KsJ db/db mice, with age-matched db/m mice on the same genetic background serving as control group. The db/db mice were randomly divided into model group, dapagliflozin (1.6 mg/kg) group, icariin high-, medium-, low-dose (120, 60, 30 mg/kg) groups, with 10 mice in each group. Drugs were given for continuously intervention over four weeks, biochemical parameters including body weight, blood glucose, urinary protein, blood lipids and serum creatinine were measured. Renal pathological changes were observed using hematoxylin-eosin staining and transmission electron microscopy. The expressions of extracellular matrix proteins [fibronectin (FN) and collagen type IV (Col-Ⅳ)] in the glomerular mesangium was assessed by immunofluorescence. Levels of inflammatory cytokines [interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)] and proteins related to high mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/nuclear factor-κB (NF-κB) signaling pathway were detected by ELISA assay and Western blotting. In vitro experiments were performed to investigate the effect of icariin on extracellular matrix protein expressions in high glucose-induced SV40 MES-13 cells. Results In vivo experiments results showed that high-dose icariin significantly reduced the body weight, urinary protein, blood lipid and serum creatinine levels in DKD mice (P < 0.01, 0.001), alleviated pathological changes such as mesangial expansion, basement membrane thickening and podocyte fusion (P < 0.001), reduced the levels of IL-1β, IL-6 and TNF-α in plasma and renal tissue (P < 0.01, 0.001), decreased the infiltration of macrophages in the kidney, and significantly inhibited the protein expressions of HMGB1, TLR2, TLR4 and p-p65 in renal tissue (P < 0.001). In vitro experiments results showed that icariin inhibited the expressions of FN and Col-Ⅳ in high glucose-induced glomerular mesangial cells. Conclusion Icariin could effectively inhibit HMGB1/TLRs/NF-κB signaling pathway, thereby attenuating renal inflammatory response and abnormal extracellular matrix accumulation, ultimately improving pathological injury in DKD.

Key words

diabetic kidney disease / icariin / inflammatory response / HMGB1/TLRs/NF-κB signaling pathway / extracellular matrix

引用本文

徐长青, 刘宗梅, 张倩, 付小燕. 淫羊藿苷通过调控HMGB1/TLRs/NF-κB信号通路和炎症反应缓解糖尿病肾病. 中草药, 2026 , 57 (13) : 5130 -5139 . DOI: 10.7501/j.issn.0253-2670.2026.13.016

XU Changqing, LIU Zongmei, ZHANG Qian, FU Xiaoyan. Icariin alleviates diabetic kidney disease by regulating HMGB1/TLRs/NF-κB signaling pathway and inflammatory response[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (13) : 5130 -5139 . DOI: 10.7501/j.issn.0253-2670.2026.13.016

基金

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咸阳市重点研发计划项目 (L2003-ZDYF-SF-027); 咸阳职业技术学院科研基金项目 (2023KJB01)

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2026年第57卷第13期

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doi: 10.7501/j.issn.0253-2670.2026.13.016

接收时间：2026-02-28
首发时间：2026-09-09

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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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