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。

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.

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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