目的 通过网络药理学分析仙旱合剂治疗排卵障碍性异常子宫出血（abnormal uterine bleeding-ovulatory dysfunction，AUB-O）的作用机制，观察仙旱合剂治疗AUB-O的临床疗效，以及从血液动力学、血清白细胞介素-17（interleukin-17，IL-17）信号通路相关因子水平的变化对其作用机制进行探讨。方法 通过网络药理学分析仙旱合剂治疗AUB-O的活性成分及作用机制。选择重庆市中医院妇科97例血热型AUB-O患者，运用随机数字表法分为对照组49例和治疗组48例。对照组患者口服宫血宁胶囊治疗，治疗组患者口服仙旱合剂治疗，治疗持续10 d。观察两组的临床疗效，比较两组治疗前后的出血量、止血时间、D-二聚体水平、血小板数量、子宫血液动力学、优势卵泡率以及血清血栓素A₂（thromboxane A₂，TXA₂）、前列环素I₂（prostaglandin I₂，PGI₂）、前列腺素E₂（prostaglandin E₂，PGE₂）、前列腺素F2α（prostaglandin F2α，PGF2α）水平及IL-17信号通路相关因子IL-6、IL-1β、基质金属蛋白酶（matrix metalloproteinase 9，MMP9）、MMP1、转录激活蛋白-1（activator protein-1，AP-1）、环氧合酶-2（cyclooxygenase-2，COX-2）、核因子-κB（nuclear factor-κB，NF-κB）的变化情况。结果 通过网络药理学发现仙旱合剂治疗AUB-O与IL-17信号通路相关。治疗组总有效率为95.8%，对照组总有效率为79.6%，两组比较差异有统计学意义（P<0.05）。治疗后，两组出血量随着治疗时间的延长均减少，第7、10天出血量比治疗前及第3天显著减少（P<0.05），第10天出血量显著少于第7天（P<0.05），第10天出血量治疗组显著少于对照组（P<0.05）；治疗组止血时间显著短于对照组（P<0.05）。治疗后，与治疗前比较，治疗组患者子宫动脉子宫动脉收缩期最大血流速度/舒张末期血流速度（S/D）、阻力指数（RI）升高，D-二聚体下降（P<0.05），对照组改善不明显，且治疗组S/D显著高于对照组（P<0.05）。治疗后，两组血小板数量与治疗前比较显著增加，且治疗组血小板数量多于对照组（P<0.05）。治疗后，治疗组优势卵泡率58.3%，对照组优势卵泡率26.5%，两组差异有统计学意义（P<0.05）。治疗后，治疗组血清PGI₂、PGE₂水平明显降低（P<0.05），两组血清PGF2α、TXA₂水平明显升高（P<0.05），且治疗组血清PGI₂水平优于对照组（P<0.05）。治疗后，治疗组血清IL-6、IL-1β、MMP9、MMP1、NF-κB、AP-1、COX-2水平与治疗前比较均显著下降（P<0.05），且治疗组血清IL-6、IL-1β、AP-1、COX-2水平与对照组比较均显著降低（P<0.05）。结论 仙旱合剂治疗AUB-O疗效确切，其止血机制与增加血小板数量使血小板聚集、增加子宫动脉血流阻力，收缩子宫螺旋动脉相关。仙旱合剂可通过IL-17信号通路中的有效靶点，降低血清炎性因子的分泌，阻断COX-2诱导PGE₂的生成，起到止血的作用。

Objective To observe the clinical efficacy of Xianhan Mixture (仙旱合剂) in the treatment of abnormal uterine bleeding-ovulatory dysfunction (AUB-O), analyze its active ingredients and signal pathway through network pharmacology, and explore the mechanism in hemodynamics and interleukin-17 (IL-17) signal pathway. Method The active ingredients and mechanism of Xianhan Mixture in the treatment of AUB-O were analyzed by network pharmacology. A total of 97 cases of hemothermic AUB-O were selected from the department of gynecology in Chongqing Hospital of Traditional Chinese Medicine. They were randomly divided into control group (49 cases) and treatment group (48 cases). The control group was given Gongxuening Capsule (宫血宁胶囊) orally, and the treatment group was given Xianhan Mixture orally for 10 d. The clinical effect of the two groups was observed. The bleeding volume, bleeding time, D-dimer level, platelet count, uterine hemodynamics, dominant follicle rate and serum thromboxane A₂ (TXA₂) and prostaglandin I₂ (PGI₂), prostaglandin E₂ (PGE₂), prostaglandin F2α (PGF2α) level and IL-17 signaling pathway related factors IL-6, IL-1β, matrix metalloproteinase 9 (MMP9), MMP1, activator protein-1 (MMP1), activator protein-1 (AP-1), cyclooxygenase-2 (COX-2), and nuclear factor-κB (NF-κB) were compared between the two groups before and after treatment. Results Through network pharmacological analysis, it was found that the treatment of AUB-O by Xianhan Mixture was related to IL-17 signaling pathway. The total effective rate was 95.8% in the treatment group and 79.6% in the control group, the treatment group was superior to the control group (P< 0.05). After treatment, the bleeding volume in the two groups decreased with the extension of treatment time, the bleeding volume in the 7th and 10th day was significantly reduced compared with that before treatment and the 3rd day (P < 0.05), the bleeding volume in the 10th day was significantly less than that in the 7th day (P < 0.05), and bleeding volume in the 10th day was significantly less than that in the control group (P < 0.05); The bleeding time in the treatment group was less than that in the control group (P < 0.05). After treatment, compared with before treatment, the maximum systolic blood velocity/end-diastolic blood velocity (S/D) and resistance index (RI) of uterine artery in the treatment group were increased, and D-dimer was decreased (P < 0.05), while the improvement was not obvious in the control group, and S/D in the treatment group was significantly higher than that in the control group (P < 0.05). After treatment, the number of platelets in the two groups was significantly increased compared with that before treatment, and the number of platelets in the treatment group was higher than that in the control group (P < 0.05). After treatment, the dominant follicle rate was 58.3% in the treatment group and 26.5% in the control group, and the difference between the two groups was statistically significant (P < 0.05). After treatment, serum PGI₂ and PGE₂ levels in the treatment group were significantly decreased (P < 0.05), serum PGF2α and TXA₂ levels in the two groups were significantly increased (P < 0.05), and serum PGI₂ levels in the treatment group were better than those in the control group (P < 0.05). After treatment, serum levels of IL-6, IL-1β, MMP9, MMP1, NF-κB, AP-1 and COX-2 in treatment group were significantly decreased compared with before treatment (P < 0.05), and serum levels of IL-6, IL-1β, AP-1 and COX-2 in treatment group were significantly decreased compared with control group (P < 0.05). Conclusion Xianhan Mixture was effective in the treatment of AUB-O, and its hemostatic mechanism was related to increasing the number of platelets, increasing the blood flow resistance of uterine artery, and shrinking the spiral artery of uterus. Xianhan Mixture could reduce the secretion of serum inflammatory factors through effective targets in IL-17 signaling pathway, block the generation of COX-2 induced PGE₂, and play a hemostatic role.

R285.64

重庆市卫生计生委中医药科技项目（ZY201602106）；重庆市中医药重点学科项目[(2018)43]；国家中医药管理局第三届国医大师传承工作室及全国名中医传承工作室（2018YFC1704104）；第七批全国老中医药专家学术经验传承项目[(2022)79]；夏敏重庆英才·创新领军人才项目[2019(2)]