中国中药杂志

基于AdipoR/AMPKα/Cpt1b信号轴探讨健脾活骨方治疗酒精性股骨头坏死的作用机制

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陈沛萍 ¹ , 黄凤玉 ¹ , 张昕卓 ¹ , 丁黛悦 ¹ , 宋常月 ¹ , 刘春芳 ¹ , 孔祥英 ¹ , 陈卫衡 ² , 苏晓慧 ¹^,^* , 林娜 ¹^,^*

中国中药杂志 | 股骨头坏死动态血瘀新知及其系统干预前沿专题 2026,51(2): 361-370

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中国中药杂志 |股骨头坏死动态血瘀新知及其系统干预前沿专题 2026 , 51 (2) : 361 -370

基于AdipoR/AMPKα/Cpt1b信号轴探讨健脾活骨方治疗酒精性股骨头坏死的作用机制

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陈沛萍¹, 黄凤玉¹, 张昕卓¹, 丁黛悦¹, 宋常月¹, 刘春芳¹, 孔祥英¹, 陈卫衡², 苏晓慧¹^,^*, 林娜¹^,^*

作者信息

^1．中国中医科学院中药研究所，北京 100700

^2．北京中医药大学第三附属医院，北京 100029

通讯作者:

林娜，博士，研究员，博士生导师，主要从事中药药性和中药药理研究，E-mail: linna888@163.com；

苏晓慧，博士，副研究员，主要从事中药药理研究，E-mail: xhsu@icmm.ac.cn

Mechanism of Jianpi Huogu Formula in treatment of alcohol-induced osteonecrosis of femoral head via AdipoR/AMPKα/Cpt1b signaling axis

Pei-ping CHEN¹, Feng-yu HUANG¹, Xin-zhuo ZHANG¹, Dai-yue DING¹, Chang-yue SONG¹, Chun-fang LIU¹, Xiang-ying KONG¹, Wei-heng CHEN², Xiao-hui SU¹^,^*, Na LIN¹^,^*

Affiliations

^1.Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

^2.Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing 100029, China

出版时间: 2026-01-15 doi: 10.19540/j.cnki.cjcmm.20251024.901

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摘要

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基于脂联素受体／5′-AMP激活蛋白激酶催化亚基α-1／肉碱棕榈酰转移酶1b（AdipoR/AMPKα/Cpt1b）信号轴，探讨健脾活骨方治疗酒精性股骨头坏死（AONFH）的作用机制。将72只SD大鼠随机分为正常组、模型组和健脾活骨方组（5.0 g·kg^-1）。除正常组外，其余2组采用46%乙醇灌胃建立AONFH模型，健脾活骨方组在造模4周后开始药物干预。分别于干预4周和8周后取材，采用Von Frey纤维丝及丙酮滴试验测定机械痛阈和冷敏痛阈；斜板实验评估下肢肌力；Micro-CT扫描并测定骨密度（BMD）、骨体积分数（BV/TV）、骨小梁厚度（Tb. Th）等骨计量学参数，HE染色观察组织病理学改变，转录组测序筛选健脾活骨方干预AONFH的差异表达基因（DEGs）并进行基因本体论（GO）功能和京都基因与基因组百科全书（KEGG）通路富集；Western blot检测股骨头组织中AdipoR1、AdipoR2、p-AMPKα及Cpt1b蛋白表达水平。结果显示，模型组大鼠在造模8周后出现机械痛阈显著降低及冷敏痛阈升高（P<0.05，P<0.01），提示痛觉超敏；斜板实验最大倾斜角度明显减小（P<0.01），提示下肢肌力减退；股骨头表面粗糙、软骨暗红区扩大，骨小梁稀疏断裂，空骨陷窝率及脂肪细胞数量显著增加（P<0.01），BMD、BV/TV、Tb. Th及骨小梁数量（Tb. N）均显著下降（P<0.01）。健脾活骨方干预4周即显著缓解机械及冷痛超敏（P<0.05），恢复下肢肌力（P<0.01），改善股骨头表面形态；8周后骨小梁结构进一步恢复，空骨陷窝率下降、脂肪细胞减少，BMD、BV/TV、Tb. Th及Tb. N显著回升（P<0.05，P<0.01），囊变及塌陷明显减轻。转录组学分析显示，健脾活骨方显著调控231个关键DEGs，显著富集于脂肪细胞因子信号通路，并且与AdipoR1、AdipoR2、p-AMPKα及Cpt1b等基因密切相关。Western blot结果表明，AONFH模型组AdipoR1、AdipoR2、p-AMPKα及Cpt1b表达较正常组显著下调（P<0.01），健脾活骨方干预后上述蛋白表达水平明显回调（P<0.05，P<0.01）。综上，该研究证实健脾活骨方可通过激活AdipoR/AMPKα/Cpt1b信号轴，改善骨髓脂质环境，改善股骨头骨微结构，从而有效缓解AONFH的疼痛及功能障碍，为临床AONFH的防治提供新的实验依据和分子靶点。

关键词

酒精性股骨头坏死 / 健脾活骨方 / 转录组学 / AdipoR/AMPKα/Cpt1b信号轴

Abstract

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Based on the adiponectin receptor/5′-AMP-activated protein kinase catalytic subunit α-1/carnitine palmitoyltransferase 1b (AdipoR/AMPKα/Cpt1b) signaling axis, this study investigated the therapeutic mechanisms of Jianpi Huogu Formula (JPHGF) in alcohol-induced osteonecrosis of the femoral head (AONFH). A total of 56 Sprague-Dawley rats were randomly divided into a normal group, a model group, and a JPHGF group (5.0 g·kg^-1). Except for the normal group, rats in the other two groups were administered 46% ethanol by gavage to establish the AONFH model, and JPHGF intervention was initiated in the treatment group at week 4 after model induction. After 4 and 8 weeks of intervention, samples were collected. Mechanical and cold pain thresholds were assessed using Von Frey filaments and the acetone drop test, respectively. Hindlimb muscle strength was evaluated by the inclined plane test. Micro-computed tomography (micro-CT) was used to determine bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb. Th), and other bone morphometric parameters. Hematoxylin-eosin (HE) staining was performed to observe histopathological changes. Transcriptomic sequencing was conducted to identify differentially expressed genes (DEGs) regulated by JPHGF in AONFH, followed by Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Western blot was used to detect the protein expression of AdipoR1, AdipoR2, phosphorylated AMPKα, and Cpt1b in femoral head tissues. The results showed that after 8 weeks of modeling, rats in the model group exhibited significantly decreased mechanical pain thresholds and increased cold sensitivity (P<0.05, P<0.01), indicating hyperalgesia. The maximum inclined angle was markedly reduced (P<0.01), suggesting weakened hindlimb muscle strength. The femoral head surface appeared rough, with enlarged dark-red cartilage areas and sparse, disrupted trabeculae; the proportion of empty lacunae and the number of adipocytes were significantly increased (P<0.01), while BMD, BV/TV, Tb. Th, and trabecular number (Tb. N) were significantly decreased (P<0.01). After 4 weeks of JPHGF intervention, mechanical and cold hyperalgesia were significantly alleviated (P<0.05), hindlimb strength was restored (P<0.01), and surface morphology of the femoral head was improved. After 8 weeks, trabecular structure was further restored, with decreased empty lacunae and reduced adipocyte numbers, and BMD, BV/TV, Tb. Th, and Tb. N significantly increased (P<0.05, P<0.01); cystic degeneration and collapse were markedly alleviated. Transcriptomic analysis revealed that JPHGF significantly regulated 231 key DEGs, which were mainly enriched in adipocytokine signaling pathways and closely associated with AdipoR1, AdipoR2, p-AMPKα, and Cpt1b. Western blot analysis showed that AdipoR1, AdipoR2, p-AMPKα, and Cpt1b expression levels were significantly downregulated in the AONFH model group compared with the normal group (P<0.01), but were markedly upregulated following JPHGF treatment (P<0.05, P<0.01). In summary, this study demonstrates that JPHGF exerts therapeutic effects against AONFH by activating the AdipoR/AMPKα/Cpt1b signaling axis, thereby improving bone marrow lipid homeostasis and restoring femoral head microarchitecture, effectively relieving pain and functional impairment. These findings provide new experimental evidence and molecular targets for the prevention and treatment of AONFH in clinical practice.

Key words

alcohol-induced osteonecrosis of the femoral head / Jianpi Huogu Formula (JPHGF) / transcriptomics / AdipoR/AMPKα/Cpt1b signaling axis

引用本文

陈沛萍, 黄凤玉, 张昕卓, 丁黛悦, 宋常月, 刘春芳, 孔祥英, 陈卫衡, 苏晓慧, 林娜. 基于AdipoR/AMPKα/Cpt1b信号轴探讨健脾活骨方治疗酒精性股骨头坏死的作用机制. 中国中药杂志, 2026 , 51 (2) : 361 -370 . DOI: 10.19540/j.cnki.cjcmm.20251024.901

Pei-ping CHEN, Feng-yu HUANG, Xin-zhuo ZHANG, Dai-yue DING, Chang-yue SONG, Chun-fang LIU, Xiang-ying KONG, Wei-heng CHEN, Xiao-hui SU, Na LIN. Mechanism of Jianpi Huogu Formula in treatment of alcohol-induced osteonecrosis of femoral head via AdipoR/AMPKα/Cpt1b signaling axis[J]. Chinese Journal of Traditional Chinese Medicine, 2026 , 51 (2) : 361 -370 . DOI: 10.19540/j.cnki.cjcmm.20251024.901

基金

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国家自然科学基金重点项目(82030122)
国家自然科学基金面上项目(82474548)

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2026年第51卷第2期

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文章信息

doi: 10.19540/j.cnki.cjcmm.20251024.901

接收时间：2025-09-16
首发时间：2026-06-25
出版时间：2026-01-15

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出版历史

收稿日期：2025-09-16

基金

国家自然科学基金重点项目(82030122)

国家自然科学基金面上项目(82474548)

作者信息

^1．中国中医科学院中药研究所，北京 100700

^2．北京中医药大学第三附属医院，北京 100029

通讯作者:

林娜，博士，研究员，博士生导师，主要从事中药药性和中药药理研究，E-mail: linna888@163.com；

苏晓慧，博士，副研究员，主要从事中药药理研究，E-mail: xhsu@icmm.ac.cn

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https://castjournals.cast.org.cn/joweb/zgzyzz/CN/10.19540/j.cnki.cjcmm.20251024.901

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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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