动物腹泻严重影响我国畜禽养殖业的发展，中兽药以其绿色环保、药效稳定受到世人的瞩目，白头翁汤是许多抗腹泻中兽药复方的基础，阐明其配伍规律及作用机制将更有利于新兽药的研发和临床应用。针对其作用机制的研究包括抗内毒素、解热、抗炎、对平滑肌作用、对肠道粘膜保护等方面，但细菌和病毒内毒素往往通过改变环核苷酸和Ca2+信号通路的活性导致Cl-分泌增加、Na+和水吸收减少引发腹泻，因此调节这些离子通道和转运体的表达和/（或）活性，包括CFTR、CaCCs、NHEs、AQPs等应该是治疗腹泻的重要途径。通过正交试验设计，对白头翁汤及其主要组分进行合理分组；研究各组对大肠杆菌性腹泻和番泻叶引发腹泻的治疗效果；探讨对肠道和肠上皮细胞系离子通道和转运体的表达和/（或）活性的影响，从而明确白头翁汤不同配伍的抗腹泻机制，为开发新兽药、提高药效、降低有效剂量和减轻副作用提供理论基础，为临床合理应用提供保障。

Animal diarrhea is a major health challenge to the development of animal husbandry in China, people has focused their attention upon veterinary traditional Chinese medicine (TCM) as their efficacy with little or no pollution to environment compared with antibiotics. Among the TCMs, Pulsatillae decoction is used most usual for the significant efficacy and is the base of many complex prescriptions. Determination of its compatibility law and action mechanism will provide supportive scientific evidence in favour of its continous usage and new veterinary TCM research. Previous studies have showed its antiendotoxin activity, relieve fever activity, anti-inflammatory activity, smooth muscle relaxant activity and mucosal protective activity, however, diarrheas caused by bacterial and viral enterotoxins, result from activation of cyclic nucleotide and/or Ca2+ signaling pathways in intestinal epithelial cells, enterocytes, which increase the permeability of Cl- channels, reduction in intestinal Na+ and water absorption at the lumen-facing membrane. Regulation of ion channels and transporters, including the cystic fibrosis transmembrane conductance regulator (CFTR) and Ca2+-activated Cl- channels (CaCCs), Na+/H+ exchangers (NHEs), aquaporin (AQPs), represents an attractive strategy for antisecretory drug therapy. Orthogonal experiment design was adopted to divide Pulsatillae decoction and its components into several groups, therapeutic efficacies of each group to diarrheas caused by Escherichia coli and caused by Folium Sennae were studied, and influences to the expression and/ or activity of ion channels and transporters in intestinal epithelial cells, enterocytes were also evaluated. To illuminate the anti-diarrhea mechanism of Pulsatillae decoction and its compatibility can provide proof-of-concept and rationale for new veterinary medicine research, elevate efficacy, depress curative dose and lighten side effect. It also can ensure reasonable usage in clinical.

中兽药在动物保健领域的作用日趋增强，针对其药效、药代动力学、作用机制等方面的研究也随之加深。白头翁汤是治疗畜禽腹泻的经典名方，本研究以白头翁汤及其拆方为研究对象，对它们的配伍规律和作用机制进行了以下几个方面的研究：（1）白头翁汤中主要成分含量的测定。（2）大肠杆菌性小鼠腹泻模型和番泻叶致小鼠腹泻模型的制备。（3）白头翁汤及其拆方抗腹泻作用研究。（4）药物对肠道离子通道、转运体表达的影响。（5）药物对主要离子通道、转运体表达影响的体外作用。（6）体外抑菌作用研究。（7）白头翁汤在山羊体内药代动力学研究。结果：（1）建立了白头翁汤中秦皮苷、秦皮素、秦皮乙素、秦皮甲素、非洲防己碱、黄连碱、巴马亭、小檗碱等8种有效成分同时检测的HPLC方法。（2）采用22-30日龄小鼠，以灌胃的方式可制备模型大肠杆菌性腹泻；日龄对番泻叶提取液制备腹泻模型没有明显影响。（3）黄连在白头翁汤抗大肠杆菌性腹泻中发挥了主要作用；白头翁、黄连在白头翁汤抗番泻叶引发腹泻中发挥了主要作用。（4）NHE3、AQP1、AQP3、AQP4在番泻叶引发腹泻过程中变化明显，并且受药物作用有显著变化，可以作为脾虚型腹泻药物研发的靶点。在大肠杆菌性腹泻中NHE2、NHE3、AQP1、AQP3、AQP4的变化显著，黄连单味药材作用尤为显著，可以对黄连进行详细研究以筛选抗细菌性腹泻药物。（5）黄连对肠道细胞NHE3、AQP3、AQP4等转录和表达都有一定的作用。（6）白头翁汤中含有抗菌成分，但对细菌的抑杀作用并不是其发挥抗细菌性腹泻作用的唯一途径。（7）秦皮甲素、秦皮苷、秦皮素、非洲防己碱、黄连碱、巴马亭、和小檗碱、在山羊体内呈现一级吸收一室模型，秦皮乙素在山羊体内呈现二室模型。结论：白头翁汤通过调控肠道离子通道、转运体的表达在动物腹泻过程中发挥重要作用，但不是唯一途径；黄连在大肠杆菌性腹泻中发挥作用明显，黄连、白头翁在番泻叶引发腹泻中作用明显，其他药味发挥着不可或缺的作用，机制有待于进一步研究。