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牛膝对血府逐瘀汤中指标成分在气滞血瘀证代谢相关脂肪性肝病大鼠体内组织分布、血浆蛋白结合和受体表达的影响

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中草药 | 药理与临床 2026,57(6): 2170-2186

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中草药 |药理与临床 2026 , 57 (6) : 2170 -2186

牛膝对血府逐瘀汤中指标成分在气滞血瘀证代谢相关脂肪性肝病大鼠体内组织分布、血浆蛋白结合和受体表达的影响

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吴贤志¹, 朱昕昀¹, 陈婧¹, 朱叶², 刘爽¹, 段新屹¹, 沈龙宇¹, 黄巍¹, 张宏¹

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吴贤志: 吴贤志,男,硕士研究生,研究方向为方剂学。E-mail:wuxianzhi@stu.cdutcm.edu.cn

Effect of Achyranthis Bidentatae Radix on tissue distribution, plasma protein binding and receptor expression of marker components in Xuefu Zhuyu Decoction in rats with metabolic liver disease related to qi stagnation and blood stasis syndrome

WU Xianzhi, ZHU Xinyun, CHEN Jing, ZHU Ye, LIU Shuang, DUAN Xinyi, SHEN Longyu, HUANG Wei, ZHANG Hong

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doi: 10.7501/j.issn.0253-2670.2026.06.015

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目的探究牛膝Achyranthis Bidentatae Radix对血府逐瘀汤中指标成分（苦杏仁苷、羟基红花黄色素A、阿魏酸、芍药苷、柚皮苷）在气滞血瘀证代谢相关脂肪性肝病大鼠体内组织分布、血浆蛋白结合率和受体表达的影响，进而探讨牛膝的引经作用机制。方法采用高脂饲料联合肾上腺素注射的方法建立气滞血瘀证代谢相关脂肪性肝病大鼠模型，造模成功后将大鼠按体质量分层分组，分别ig血府逐瘀汤全方、血府逐瘀汤减桔梗方、血府逐瘀汤减牛膝方及血府逐瘀汤减桔梗牛膝方。血浆蛋白结合率和受体表达实验中大鼠于给药后10 、30 min经腹主动脉采血后处死，并取脑、心、肺、肝、肾组织。组织分布实验中大鼠于给药后10、30、60 min处死，取脑、心、肺、肝、肾组织。通过高效液相色谱-质谱联用（high performance liquid chromatography-mass spectrometry，HPLC-MS）技术检测指标成分在大鼠各组织中的浓度，并对大鼠血浆中各指标成分进行定性定量分析，计算各成分的血浆蛋白结合率；采用ELISA检测各组织样本中的血小板活化因子（platelet activating factor，PAF）、腺苷A1受体、P2Y12受体和内皮素A受体表达情况。结果牛膝能降低血府逐瘀汤中苦杏仁苷、羟基红花黄色素A、阿魏酸、柚皮苷在模型大鼠体内的血浆蛋白结合率，同时增加苦杏仁苷、芍药苷在大鼠脑、肝中的分布，羟基红花黄色素A在肝、肾中的分布，阿魏酸在脑、心、肝、肾中的分布，柚皮苷在肝、肾中的分布；并且增加脑、心、肝中腺苷A1受体和脑、心、肾中P2Y12受体含量，降低脑、心、肝、肾中PAF和脑、心、肺中内皮素A受体含量。结论牛膝能降低苦杏仁苷、羟基红花黄色素A、阿魏酸、柚皮苷在大鼠体内的血浆蛋白结合率，增加其在对应组织中的含量，从而增强各成分对相应受体的影响，最终导致受体在每个组织中表达增强或减弱，协同发挥治疗血瘀证的作用，这可能是牛膝在血府逐瘀汤中发挥引经作用的机制之一。

关键词

牛膝 / 血府逐瘀汤 / 组织分布 / 血浆蛋白结合 / 受体表达 / 气滞血瘀证 / 代谢相关脂肪性肝病 / 苦杏仁苷 / 羟基红花黄色素A / 阿魏酸 / 芍药苷 / 柚皮苷

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Objective To investigate the effects of Niuxi (Achyranthis Bidentatae Radix, ABR) on tissue distribution, plasma protein binding rate and receptor expression of marker components (amygdalin, hydroxysafflor yellow A, ferulic acid, paeoniflorin, naringin) from Xuefu Zhuyu Decoction (血府逐瘀汤, XFZYD) in rats with metabolic-associated fatty liver disease (MAFLD) of qi stagnation and blood stasis syndrome (QS-BSS), and to further clarify the mechanism underlying its meridian-guiding effect. Methods A rat model of MAFLD with QS-BSS was established by high-fat diet combined with adrenaline injection. After successful modeling, rats were stratified and grouped by body weight, followed by intragastric administration of XFZYD (full formula), XFZYD without Jiegeng (Platycodonis Radix, PR), XFZYD without ABR, and XFZYD without both PR and ABR. For the plasma protein binding rate and receptor expression experiments, abdominal aortic blood was collected at 10, 30 min after a single administration, after which rats were euthanized for the collection of brain, heart, lung, liver, and kidney tissues. For the tissue distribution experiment, rats were euthanized at 10, 30, 60 min after a single administration, with the same tissues collected as above. The concentrations of marker components in tissues were determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Qualitative and quantitative analyses of these components in plasma were performed to determine their plasma protein binding rates. The expression levels of platelet-activating factor (PAF) and receptors including adenosine A1 receptor (A1R), P2Y12 receptor, and endothelin A receptor (ETAR) in tissues were measured by ELISA. Results ABR decreased the plasma protein binding rates of amygdalin, hydroxysafflor yellow A, ferulic acid, and naringin in model rats. Meanwhile, ABR increased the distribution of amygdalin and paeoniflorin in the brain and liver, hydroxysafflor yellow A in the liver and kidney, ferulic acid in the brain, heart, liver, and kidney, and naringin in the liver and kidney. Furthermore, ABR upregulated the expression levels of A1R in brain, heart, and liver as well as P2Y12 receptor in the brain, heart, and kidney, while downregulating the expression level of PAF in brain, heart, liver, and kidney and the expression level of ETAR in brain, heart and lung. Conclusion ABR could reduce the plasma protein binding rates of amygdalin, hydroxysafflor yellow A, ferulic acid and naringin in MAFLD-QS-BSS rats, thereby increasing the distribution of these components in the corresponding tissues, enhancing the effect of each component on the related receptors, and ultimately regulating the upregulation or downregulation of receptor expression in various tissues, which synergistically exerts the therapeutic effect against QS-BSS. This may be one of the mechanisms by which ABR exerts its meridian-guiding effect in XFZYD.

Key words

Achyranthis Bidentatae Radix / Xuefu Zhuyu Decoction / tissue distribution / plasma protein binding / receptor expression / qi stagnation and blood stasis syndrome / metabolic-associated fatty liver disease / amygdalin / hydroxysafflor yellow A / ferulic acid / paeoniflorin / naringin

引用本文

吴贤志, 朱昕昀, 陈婧, 朱叶, 刘爽, 段新屹, 沈龙宇, 黄巍, 张宏. 牛膝对血府逐瘀汤中指标成分在气滞血瘀证代谢相关脂肪性肝病大鼠体内组织分布、血浆蛋白结合和受体表达的影响. 中草药, 2026 , 57 (6) : 2170 -2186 . DOI: 10.7501/j.issn.0253-2670.2026.06.015

WU Xianzhi, ZHU Xinyun, CHEN Jing, ZHU Ye, LIU Shuang, DUAN Xinyi, SHEN Longyu, HUANG Wei, ZHANG Hong. Effect of Achyranthis Bidentatae Radix on tissue distribution, plasma protein binding and receptor expression of marker components in Xuefu Zhuyu Decoction in rats with metabolic liver disease related to qi stagnation and blood stasis syndrome[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (6) : 2170 -2186 . DOI: 10.7501/j.issn.0253-2670.2026.06.015

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国家自然科学基金资助项目 (82574911); 国家自然科学基金资助项目 (82360917); 邓中甲名老中医特色诊疗经验总结及学术思想传承研究

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Guo X Y, Yin X Z, Liu Z J, et al. Non-alcoholic fatty liver disease (NAFLD) pathogenesis and natural products for prevention and treatment[J]. Int J Mol Sci, 2022, 23(24): 15489.
Younossi Z, Anstee Q M, Marietti M, et al. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(1): 11-20.
Cui S J, Ye J. MAFLD: A ferroptotic disease[J]. Trends Mol Med, 2025, doi: 10.1016/j.molmed.2025.08.006.
中国中西医结合学会消化系统疾病专业委员会. 非酒精性脂肪性肝病中西医结合诊疗专家共识(2025年)[J]. 中国中西医结合消化杂志, 2025, 33(4): 339-350.
张颖, 谈燕清, 刘杰, 等. 青钱柳总三萜通过调节FXR介导的胆汁酸和脂质代谢途径改善高脂饮食诱导的小鼠代谢相关脂肪性肝病[J]. 中草药, 2026, 57(3): 949-967.
杨会珍. 血府逐瘀汤调节慢性气滞血瘀大鼠模型的物质基础研究[D]. 北京: 中国中医科学院, 2022.
范建高, 徐小元, 南月敏, 等. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)[J]. 实用肝脏病杂志, 2024, 27(4): 494-510.
高艳艳, 薛茹云, 徐芳莹, 等. 茵陈蒿汤成分配伍对高脂诱导小鼠代谢相关脂肪性肝病的治疗作用[J/OL].浙江大学学报: 医学版, (2025-11-19)[2025-11-28]. https://link.cnki.net/urlid/33.1248.R.20251118.1738.002.
刘楠, 姜云耀, 李莹, 等. 气滞血瘀证动物模型研究现状[J]. 中国实验方剂学杂志, 2018, 24(1): 217-226.
梅姗姗, 黄苗苗, 黄楚莹, 等. 基于代谢组学及肠道菌群的水蛭治疗气滞血瘀证大鼠作用机制探究[J]. 中国现代中药, 2025, 27(5): 878-889.
郭文鹤, 黄娜娜, 张晓亮, 等. 动脉粥样硬化(气滞血瘀证)病证结合大鼠模型的研究[J]. 中国比较医学杂志, 2019, 29(9): 32-41.
陈思琦, 刘德鸿, 黄东, 等. 超滤法结合高效液相色谱法测定枳实中两个生物碱在不同种属生物中的血浆蛋白结合率[J]. 中国药学杂志, 2023, 58(15): 1410-1415.
董靓, 陈伶利, 李杰. 从“血道由肝”理论探析动脉粥样硬化的病机与治疗[J]. 北京中医药大学学报, 2025, 48(7): 966-972.
张德珂, 聂金娥, 钱芳芳. 中药苦杏仁药理作用研究进展[J]. 山东化工, 2021, 50(22): 100-102.
牛芬溪, 刘悦, 刘雅楠, 等. 羟基红花黄色素A的药理作用及研究进展[J]. 中国药学杂志, 2021, 56(17): 1372-1377.
李秀阳, 张天资. 羟基红花黄色素A的临床药理研究进展[J]. 中国现代医药杂志, 2025, 27(5): 36-42.
刘平, 赵俊超, 李日光. 芍药苷药理作用及其机制研究进展[J]. 中医药导报, 2023, 29(8): 84-88.
陈园, 杜利新, 李涛, 等. 芍药苷对心血管疾病的药理作用及其新型药物制剂的研究进展[J]. 湖南中医药大学学报, 2025, 45(7): 1394-1400.
唐潇潇, 温伟烜, 李佳乐, 等. 阿魏酸药理活性研究进展[J]. 广州化工, 2024, 52(6): 22-25.
刘丹, 苗加伟, 谭子豪, 等. 柚皮苷对心血管疾病的药理作用研究进展[J]. 中国临床药理学与治疗学, 2025, 30(2): 272-281.
信琪琪. 基于腺苷A_1受体探讨芍药苷促血管新生作用[D]. 北京: 北京中医药大学, 2016.
臧宝霞, 金鸣, 司南, 等. 羟基红花黄色素A对血小板活化因子的拮抗作用[J]. 药学学报, 2002, 37(9): 696-699.
黄瑾, 胡晋红, 朱全刚. 阿魏酸及其衍生物的药理作用[J]. 中药材, 2001, 24(7): 522-526.
刘彦茹. 阿魏酸钠对冠心病的疗效及对血管内皮功能的保护作用分析[J]. 当代临床医刊, 2022, 35(3): 10-11.
黄曼婷. 柚皮素通过P2Y₁₂受体信号通路抑制血小板活性和动脉血栓形成[D]. 广州: 广州中医药大学, 2017.
Wen Q Y, Yu S, Wang S S, et al. Impact of intestinal microbiota on metabolic toxicity and potential detoxification of amygdalin[J]. Front Microbiol, 2022, 13: 1030516.
王炯文, 季笑遥, 陈可禧, 等. 皂苷表面活性剂在药物递送系统中的研究进展[J]. 药学研究, 2024, 43(8): 793-797.
谭滢, 韩宝瑾, 钟毅薇, 等. 基于湿浊三焦传变探讨肺癌胸腔积液的治疗思路[J]. 中医杂志, 2025, 66(21): 2287-2291.

2026年第57卷第6期

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doi: 10.7501/j.issn.0253-2670.2026.06.015

接收时间：2025-10-27
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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