目的 基于功能动物模型对消痔丸进行拆方研究，阐释消痔丸发挥止血、润肠通便、补气固脱的配伍规律。方法 在各功能实验中，动物分组为对照组、模型组（除止血功能实验）、阳性药组及消痔丸全方组、止血组与非止血组（止血功能实验）、润肠通便组与非润肠通便组（润肠通便功能实验）、补气固脱组与非补气固脱组（补气固脱功能实验）。止血功能实验中，采用大鼠断尾溢血模型，测定各给药组对大鼠出血时间长短与凝血功能指标凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）的影响。润肠通便功能实验中，采用复方地芬诺酯诱导小鼠便秘模型，测定各给药组对小鼠排便功能指标及血浆中P物质（SP）、5-羟色胺（5-HT）及血管活性肠肽（VIP）水平的影响。补气固脱功能实验中，采用游泳劳损联合放血法共同诱导气血亏虚大鼠模型，测定各给药组对大鼠表观评分、体质量、游泳时间，外周血象指标白细胞（WBC）、血红蛋白（HGB）、血小板（PLT）与红细胞（RBC）与免疫造血指标红细胞生成素（EPO）、血小板生成素（TPO）与粒细胞-巨噬细胞集落刺激因子（GM-CSF）及免疫器官脏器系数的影响。结果 与对照组相比，消痔丸全方组与止血组均能显著降低出血时间（P＜0.001）并提高出血时间缩短率（P＜0.001），其作用机制可能与抑制PT水平（P＜0.05）、促进FIB水平（P＜0.05）有关，非止血组对大鼠出血时间与凝血四项指标无显著改善作用。与模型组相比，润肠通便组小鼠排出首粒黑便时间显著缩短（P＜0.05），6 h内排便数量、排便质量及粪便含水率均显著升高（P＜0.05、0.001），同时能够上调SP与5-HT水平（P＜0.05），下调VIP水平（P＜0.01），整体效果略弱于消痔丸全方组，而非润肠通便组只能显著降低VIP水平（P＜0.05），对SP与5-HT及排便功能指标无显著性影响。与模型组相比，补气固脱组对气血亏虚大鼠具有较好的改善作用，表现为降低表观评分（P＜0.001）、延长游泳时间（P＜0.001）、提升脾脏指数（P＜0.05）、升高大鼠血液中PLT水平（P＜0.05）、降低血浆中EPO水平（P＜0.01），并提高TPO与GM-CSF水平（P＜0.01、0.001），整体效果强于消痔丸全方组；而非补气固脱组虽能降低表观评分（P＜0.05）、延长游泳时间（P＜0.05）、升高血浆中TPO与GM-CSF水平（P＜0.01、0.001），但整体作用效果弱于补气固脱组，且对大鼠外周血象指标及免疫器官脏器系数无显著改善作用。结论 白及、动物大肠、三颗针皮（炒炭）、槐角（蜜炙）、地榆（炒炭）为消痔丸发挥止血功能的主要药味；火麻仁（炒黄）、大黄（酒炒）、当归（酒炒）为消痔丸发挥润肠通便功能的主要药味；黄芪、白术（炒）、当归（酒炒）、动物大肠为消痔丸发挥补气固脱功能的主要药味。

Objective To conduct a formula dismantling study on Xiaozhi Pills (消痔丸) based on functional animal models, and elucidate the compatibility regularity by which Xiaozhi Pills exert hemostatic, laxative, and qi-tonifying and collapse-preventing effects. Methods In the functional experiments, the animal groups were categorized as follows: control group, model group (except the hemostatic function experiment), positive drug group, Xiaozhi Pills group, hemostatic and non-hemostatic groups (for the hemostatic function experiment), moisten dryness and promote bowel movements and non-moisten dryness and promote bowel movements groups (for the moisten dryness and promote bowel movements function experiment), and tonify qi to prevent collapse and non-tonify qi to prevent collapse groups (for the tonify qi to prevent collapse function experiment). In the hemostatic function experiment, a rat tail amputation model was used to determine the effects of each treatment group on bleeding time and coagulation parameters, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) levels. In the moisten dryness and promote bowel movements experiment, a composite difenoxin-induced constipation model in mice was utilized to assess the impact of each treatment group on bowel movement metrics and the expression of substance P (SP), 5-hydroxytryptamine (5-HT), and vasoactive intestinal peptide (VIP) in plasma. In the tonify qi to prevent collapse experiment, a swimming fatigue model combined with bloodletting was employed to induce a dual deficiency of qi and blood in rats, evaluating the effects of each treatment group on phenotypic scores, body weight, swimming duration, peripheral blood indices white blood cells (WBC), hemoglobin (HGB), platelets (PLT), and red blood cells (RBC), as well as hematopoietic immunological markers, including erythropoietin (EPO), thrombopoietin (TPO), and granulocyte-macrophage colony-stimulating factor (GM-CSF), along with the organ coefficients of immune organs.Results Compared with the control group, the Xiaozhi Pills group and the hemostatic group significantly reduced bleeding time in rats (P < 0.001) and increased the rate of bleeding time reduction (P < 0.001), potentially by inhibiting prothrombin time (PT) expression (P < 0.05) and promoting fibrinogen (FIB) expression (P < 0.05). In contrast, the non-hemostatic group exhibited no significant improvements in bleeding time or coagulation parameters. Furthermore, compared with the model group, the moisten dryness and promote bowel movements group significantly shortened the time to expel the first pellet of black feces (P < 0.05) and increased both the number of pellets expelled in 6 hours and fecal weight, while also enhancing fecal moisture content (P < 0.05, 0.001). This group upregulated SP and 5-HT expression (P < 0.05) and downregulated VIP expression (P < 0.01). Overall, its effects were weaker than those of the Xiaozhi Pills group, while the non-moisten dryness and promote bowel movements group only significantly reduced VIP expression (P < 0.05) and no significant effect on SP, 5-HT, or bowel function metrics (P < 0.05). Compared with the model group, the tonify qi to prevent collapse group showed notable improvements in qi and blood deficiency rats, as evidenced by a reduced apparent score (P < 0.001), prolonged swimming time (P< 0.001), increased spleen index (P < 0.05), elevated PLT levels (P < 0.05), decreased plasma EPO expression (P < 0.01), and increased TPO and GM-CSF levels (P < 0.01, 0.001). Overall, this effect was stronger than that of the Xiaozhi Pills group. Although the non-tonify qi to prevent collapse group could reduce the apparent score (P < 0.05), extend swimming time (P < 0.05), and elevate plasma TPO and GM-CSF levels (P < 0.01, 0.001), its overall effects were weaker than those of the tonify qi to prevent collapse group, with no significant improvements in peripheral blood indices, or immune organ coefficients (P < 0.05). Conclusion Baiji (Bletillae Rhizoma), Dongwudachang (Sus scrofa domestica Brisson), charred Sankezhenpi (Berberidiss Cortex), honey-fried Huaijiao (Sophorae Fructus), and charred Diyu (Sanguisorbae Radix) are the primary ingredients of Xiaozhi Pills that contribute to its hemostatic function. Charred Huomaren (Cannabis Fructus), wine-fried Dahuang (Rhei Radix et Rhizoma), and wine-fried Danggui (Angelicae Sinensis Radix) serve as the main components for moisten dryness and promote bowel movements. Huangqi (Rhei Radix et Rhizoma), charred Baizhu (Atractylodis Macrocephalae Rhizoma), wine-fried Danggui, and Dongwudachang are the key ingredients that enhance tonify qi to prevent collapse in Xiaozhi Pills.

R285.5

国有资本经营预算支持省属企业科研项目（2024GZ031）