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基于“异类相制”理论探讨淫羊藿和女贞子对补骨脂诱导肾阴虚大鼠肝损伤的影响及作用机制

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中草药 | 药理与临床 2026,57(1): 126-137

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中草药 |药理与临床 2026 , 57 (1) : 126 -137

基于“异类相制”理论探讨淫羊藿和女贞子对补骨脂诱导肾阴虚大鼠肝损伤的影响及作用机制

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李宇辉^1,2,3, 张明亮^2,3, 陈小菲^2,3, 孟高全³, 李明格³, 张辉², 吴娅丽², 杨柳青², 肖小河^1,4, 唐进法^2,3

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肖小河

作者简介:

李宇辉: 李宇辉,博士研究生,主要从事中药安全用药研究。E-mail:liyuhui@hactcm.edu.cn 张明亮: 张明亮,副主任药师,硕士生导师,主要从事中药合理用药研究。E-mail:mlzhangedu@126.com

Effect and mechanism of Epimedii Folium and Ligustri Lucidi Fructus on Psoraleae Fructus-induced liver injury based on theory of “heterogeneous medicinals mutual restriction”

LI Yuhui, ZHANG Mingliang, CHEN Xiaofei, MENG Gaoquan, LI Mingge, ZHANG Hui, WU Yali, YANG Liuqing, XIAO Xiaohe, TANG Jinfa

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doi: 10.7501/j.issn.0253-2670.2026.01.013

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目的基于“异类相制”理论，探究淫羊藿Epimedii Folium和女贞子Ligustri Lucidi Fructus对补骨脂Psoraleae Fructus诱导肾阴虚模型大鼠肝损伤的影响及作用机制。方法以补骨脂诱导的肾阴虚模型大鼠肝损伤为参照，分别给予淫羊藿和女贞子进行干预，通过体质量、肛温、粪便含水量及血清环磷酸腺苷（cyclic adenosine monophosphate，cAMP）/环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）比值评估肾阴虚指征变化情况；通过血清中丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）活性及肝组织苏木素-伊红（hematoxylin-eosin，HE）染色评估肝脏功能变化；结合代谢组学、关联分析、ROC分析及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析解析潜在机制。结果淫羊藿可显著降低模型大鼠体质量和粪便含水量（P＜0.05、0.01），显著升高肛温、cAMP/cGMP比值、ALT及AST活性（P＜0.05、0.001），并加重肝脏炎性细胞浸润，加剧肝损伤；女贞子则可显著逆转上述变化。代谢组学鉴定出17个淫羊藿和女贞子差异调控的共同代谢物，关联分析及ROC分析进一步发现神经酰胺、牛磺胆酸等6个诊断效能良好的差异代谢物，主要涉及亚油酸代谢、鞘脂代谢等8条通路。此外，淫羊藿可显著升高模型大鼠血清中炎性因子白细胞介素-1β（interleukin-1β，IL-1β）、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平（P＜0.05），并降低抗炎因子IL-10水平；女贞子则逆转上述变化。结论淫羊藿和女贞子可能通过差异调控肝脏亚油酸代谢等影响炎性细胞因子水平，从而导致补骨脂诱导的肾阴虚模型大鼠肝脏出现毒/效作用差异。为中医“异类相制”理论提供实验依据，并为补骨脂减毒增效研究提供借鉴。

关键词

异类相制 / 补骨脂 / 肝损伤 / 淫羊藿 / 女贞子 / 代谢组学 / 神经酰胺 / 牛磺胆酸 / 磷脂酰肌醇 / 7-脱氢胆固醇 / β-D-葡萄糖醛酸苷 / 亚油酸

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Objective To explore the effect and mechanism of Yinyanghuo (Epimedii Folium) and Nüzhenzi (Ligustri Lucidi Fructus) on Buguzhi (Psoraleae Fructus)-induced liver injury in a rat model of kidney-yin deficiency based on the theory of “heterogeneous medicinals mutual restriction”. Methods The liver injury rats with kidney-yin deficiency model induced by Psoraleae Fructus was taken as a reference, Epimedii Folium and Ligustri Lucidi Fructus were respectively given for intervention, the changes in indicators of kidney-yin deficiency were evaluated by through body weight, anal temperature, fecal water content and cyclic adenosine monophosphate (cAMP)/cyclic guanosine monophosphate (cGMP) ratio in serum. The changes in liver function were evaluated by measuring the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, as well as by staining liver tissue with hematoxylin eosin (HE). Metabolomics, association analysis, ROC analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were combined to elucidate potential mechanisms. Results Epimedii Folium significantly decreased body weight and fecal water content in model rats (P < 0.05, 0.01), significantly increased anal temperature, cAMP/cGMP ratio and activities of ALT, AST (P < 0.05, 0.001), aggravated the infiltration of inflammatory cells in liver and exacerbated liver damage. Ligustri Lucidi Fructus significantly reversed the above changes. Metabolomics identified 17 common metabolites that were differentially regulated between Epimedii Folium and Ligustri Lucidi Fructus. Association analysis and ROC analysis further revealed six differential metabolites with good diagnostic efficacy, including ceramide and taurocholic acid, mainly involving eight pathways such as linoleic acid metabolism and sphingolipid metabolism. In addition, Epimedii Folium could significantly increase the levels of inflammatory factors such as interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) in serum of model rats (P < 0.05), and decrease anti-inflammatory factor IL-10 level. Ligustri Lucidi Fructus reversed the above changes. Conclusion Epimedii Folium and Ligustri Lucidi Fructus may affect the levels of inflammatory cytokines by differentially regulating liver linoleic acid metabolism, leading to differences in toxicity/efficacy in liver of rats with kidney-yin deficiency induced by Psoraleae Fructus. This study provides experimental basis for the theory of “heterogeneous medicinals mutual restriction” in traditional Chinese medicine, and provides reference for the research on reducing toxicity and increasing efficiency of Psoraleae Fructus.

Key words

heterogeneous medicinals mutual restriction / Psoraleae Fructus / liver injury / Epimedii Folium / Ligustri Lucidi Fructus / metabolomics / ceramide / taurocholic acid / phosphatidylinositol / 7-dehydrocholesterol / β-D-glucuronoside / linoleic acid

引用本文

李宇辉, 张明亮, 陈小菲, 孟高全, 李明格, 张辉, 吴娅丽, 杨柳青, 肖小河, 唐进法. 基于“异类相制”理论探讨淫羊藿和女贞子对补骨脂诱导肾阴虚大鼠肝损伤的影响及作用机制. 中草药, 2026 , 57 (1) : 126 -137 . DOI: 10.7501/j.issn.0253-2670.2026.01.013

LI Yuhui, ZHANG Mingliang, CHEN Xiaofei, MENG Gaoquan, LI Mingge, ZHANG Hui, WU Yali, YANG Liuqing, XIAO Xiaohe, TANG Jinfa. Effect and mechanism of Epimedii Folium and Ligustri Lucidi Fructus on Psoraleae Fructus-induced liver injury based on theory of “heterogeneous medicinals mutual restriction”[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (1) : 126 -137 . DOI: 10.7501/j.issn.0253-2670.2026.01.013

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国家自然科学基金面上资助项目 (82173993,82574685); 中原科技创新领军人才项目 (254000510038); 河南省高校科技创新团队 (23IRTSTHN026); 河南省医学科技攻关计划项目 (SBGJ202403040); 河南省卫生健康委员会国家中医药传承创新中心联合共建科研专项 (2024ZXZX1179)

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Ge F L, Niu M, Han Z X, et al. Landscape of hepatobiliary adverse drug reactions related to preparations containing Psoraleae Fructus and its application in pharmacovigilance[J]. Chin J Integr Med, 2021, 27(11):832-837.
张潇予,王丹妮,柴欣,等.补骨脂的质量特征解析及其在减毒工艺中的应用[J]. 中草药, 2024, 55(8):2784-2791.
Zhang M L, Zhao X, Li W X, et al. Yin/Yang associated differential responses to Psoralea corylifolia Linn. in rat models:An integrated metabolomics and transcriptomics study[J]. Chin Med, 2023, 18(1):102.
吴晓燕,赫俊杰,阎星旭,等.基于“有故无殒”的补骨脂对不同肾虚证模型大鼠肝脏功能的影响[J]. 中草药, 2023, 54(2):434-441.
裴天仙,李福珍,陈梦颖,等.补骨脂素对正常大鼠和阴虚大鼠肝脏毒性差异研究及机制初探[J]. 中国药理学通报, 2025, 41(5):843-850.
周学平,冯哲,俞志超,等.“异类相制”理论及其指导下的有毒中药应用策略[J]. 中医杂志, 2024, 65(5):449-454.
张明亮,赵旭,李伟霞,等.补骨脂“大燥伤肝”的客观性及生物学机制研究[J]. 药学学报, 2023, 58(4):1014-1023.
张明亮.基于病证毒理学的补骨脂毒-效转化与精准用药策略研究[D]. 成都:成都中医药大学, 2023.
王赛,白明,苗明三.阴虚证动物模型诊断指标及分析[J]. 中国比较医学杂志, 2021, 31(1):132-137.
de Gaetano M, Alghamdi K, Marcone S, et al. Conjugated linoleic acid induces an atheroprotective macrophage MΦ2 phenotype and limits foam cell formation[J]. J Inflamm, 2015, 12:15.
周学平,周玲玲,朱华旭,等.从物质-代谢-毒性关联视角多维度解析雷公藤复方配伍“异类相制”减轻肝损伤机制[J]. 南京中医药大学学报, 2020, 36(6):795-798.
Summers S A, Chaurasia B, Holland W L. Metabolic messengers:Ceramides[J]. Nat Metab, 2019, 1(11):1051-1058.
Liu Z M, Zhang Z F, Huang M, et al. Taurocholic acid is an active promoting factor, not just a biomarker of progression of liver cirrhosis:Evidence from a human metabolomic study and in vitro experiments[J]. BMC Gastroenterol, 2018, 18(1):112.
乐英彪,王昆华,邹雷.牛磺胆酸促进肝硬化发展的机制[J]. 临床肝胆病杂志, 2021, 37(11):2658-2662.
Gomez-Larrauri A, Larrea-Sebal A, Martín C, et al. The critical roles of bioactive sphingolipids in inflammation[J]. J Biol Chem, 2025, 301(8):110475.
Chen X, Cai X D, Le R R, et al. Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses[J]. Biochem Biophys Res Commun, 2018, 496(2):245-252.
Zhou S, Gu J, Liu R, et al. Spermine alleviates acute liver injury by inhibiting liver-resident macrophage proinflammatory response through ATG5-dependent autophagy[J]. Front Immunol, 2018, 9:948.
Freitas F P, Alborzinia H, Dos Santos A F, et al. 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis[J]. Nature, 2024, 626(7998):401-410.
Shi Q, Haenen G R, Maas L, et al. Inflammationassociated extracellular β-glucuronidase alters cellular responses to the chemical carcinogen benzo[a] pyrene[J]. Arch Toxicol, 2016, 90(9):2261-2273.
Zhang Q, Jiang Y, Qin Y, et al. Linoleic acid alleviates lipopolysaccharide induced acute liver injury via activation of Nrf2[J]. Physiol Res, 2024, 73(3):381-391.
Warner D R, Liu H L, Miller M E, et al. Dietary linoleic acid and its oxidized metabolites exacerbate liver injury caused by ethanol via induction of hepatic proinflammatory response in mice[J]. Am J Pathol, 2017,187(10):2232-2245.
Kikut J, Komorniak N, Ziętek M, et al. Inflammation with the participation of arachidonic(AA)and linoleic acid(LA)derivatives(HETEs and HODEs)is necessary in the course of a normal reproductive cycle and pregnancy[J]. J Reprod Immunol, 2020, 141:103177.
Liu Z X, Li Z Z, Guo Y Y, et al. The protective effects of Propolis against lipopolysaccharide-induced acute liver injury by modulating serum metabolites and gut flora[J]. Sci Rep, 2025, 15(1):16959.
Zhu Y R, Yang Y Q, Ruan D D, et al. Paeoniflorin attenuates APAP-induced liver injury via intervening the crosstalk between hepatocyte pyroptosis and NETs[J]. Int J Mol Sci, 2025, 26(4):1493.
王中一,张治杰,姚亚乐,等.连翘叶乙醇提取物对APAP诱导肝损伤小鼠氧化应激及炎症因子的影响[J]. 甘肃农业大学学报, 2024, 59(4):1-8.

2026年第57卷第1期

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doi: 10.7501/j.issn.0253-2670.2026.01.013

接收时间：2025-10-09
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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