目的 基于功能动物模型对消痔丸进行拆方研究，阐释消痔丸发挥清热消肿、止痛、生肌的配伍规律。方法 在各功能实验中，动物分组分别为对照组、模型组、阳性药组、消痔丸全方组、清热消肿止痛组与非清热消肿止痛组（清热消肿功能实验与清热止痛功能实验）及消肿生肌组与非消肿生肌组（消肿生肌功能实验）。清热消肿功能实验中，采用巴豆油诱导小鼠耳肿胀模型，测定各给药组对小鼠耳肿胀率、肿胀抑制率及耳组织中炎症因子一氧化氮（NO）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平的影响。清热止痛功能实验中，采用稀醋酸诱导小鼠扭体反应及腹腔毛细血管通透性亢进模型，测定各给药组对小鼠扭体反应次数、扭体反应抑制率及腹腔毛细血管通透性抑制率的影响。消肿生肌功能实验中，采用醋酸建立大鼠肛门溃疡模型，评估各给药组大鼠肛门溃疡表观评分并测定大鼠肛门溃疡面积及表皮生长因子（EGF）、基质金属蛋白酶-9（MMP-9）水平。结果 与模型组相比，清热消肿止痛组能够显著改善耳肿胀率与耳肿胀抑制率（P＜0.05），其效果弱于消痔丸全方组，作用机制可能为抑制耳组织中NO、IL-1β水平（P＜0.05）；与模型组相比，清热消肿止痛组均能显著减少小鼠扭体反应次数（P＜0.001），提高扭体反应抑制率（P＜0.001）与腹腔毛细血管通透性抑制率（P＜0.01），而非清热消肿止痛组对以上指标均无显著改善作用。与模型组相比，第7天消肿生肌组能够显著改善大鼠肛门表观评分（P＜0.01），至给药第9天表观评分及溃疡面积治疗评价上仍具有良好的效果（P＜0.05、0.001），整体治疗效果弱于消痔丸全方，作用机制可能为促进EGF表达（P＜0.001）并抑制MMP-9表达（P＜0.001），非消肿生肌组只有抑制MMP-9表达的作用（P＜0.001）。结论 地榆（炒炭）、牡丹皮、三颗针皮（炒炭）、大黄（酒炒）、防己、槐角（蜜炙）为消痔丸发挥清热消肿止痛功能的主要药味，黄芪、白及、动物大肠为消痔丸发挥消肿生肌功能的主要药味。

Objective To conduct a formula dismantling study on Xiaozhi Pills based on functional animal models, and elucidate the heat-clearing and swelling-reducing, analgesic, and wound-healing-promoting effects. Methods In each functional experiment, animals were divided into control group, model group, positive drug group, Xiaozhi Pills group, heat-clearing and detumescence group, and non-heat-clearing and detumescence group (for both clearing heat for detumescence experiments and clear away heat and alleviate pain experiments); detumescent and granulation-promoting group versus non-detumescent and granulation-promoting group (for detumescence and promoting granulation experiment). In the clearing heat for detumescence experiment, croton oil was used to establish the mouse ear swelling model, and the ear edema rate, edema inhibition rate, and the levels of inflammatory factors including nitric oxide (NO), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in ear tissues of each group were measured. In the experiment designed to clear heat and alleviate pain, a dilute acetic acid-induced mouse writhing response model, along with an intraperitoneal capillary permeability assessment, was employed to evaluate the effects of each treatment group on the writhing times, writhing inhibition rate and inhibition rate of peritoneal capillary permeability. In the experiment aimed at detumescence and promoting granulation, an acetic acid-induced anal ulcer model in rats was established to assess the macroscopic score of anal ulcers and the ulcer area, as well as the levels of epidermal growth factor (EGF) and matrix metalloproteinase-9 (MMP-9) in the treatment groups. Results Compared with the model group, the heat-clearing and detumescence group significantly reduced ear edema rate and elevated edema inhibition rate (P < 0.05) with weaker efficacy than the Xiaozhi Pills group. Its mechanism may be related to down-regulating NO and IL-1β levels in ear tissues (P < 0.05). Compared with the model group, the heat-clearing and detumescence group markedly decreased writhing times (P < 0.001) and increased writhing inhibition rate (P < 0.001) and intraperitoneal capillary permeability (P < 0.01), while the non-heat-clearing and detumescence group showed no significant improvements in these metrics. Compared with the model group, on day 7 after administration, the detumescent and granulation-promoting group significantly reduced the macroscopic scores in rats (P< 0.01). Satisfactory therapeutic effects on macroscopic scores and ulcer area were still observed on day 9 (P < 0.05, 0.01), though the overall efficacy was inferior to the Xiaozhi Pills group. Its potential mechanism involved up-regulating EGF expression (P< 0.001) and inhibiting MMP-9 expression (P < 0.001). In contrast, the non-detumescent and granulation-promoting group only inhibited MMP-9 expression (P < 0.001). Conclusion Carbonized Sanguisorbae Radix, Moutan Cortex, carbonized Berberidiss Cortex, wine-processed Rhei Radix et Rhizoma, Stephaniae Tetrandrae Radix and honey-fried Sophorae Fructus are the principal medicinal herbs responsible for the heat-clearing and detumescence effects of Xiaozhi Pills; Astragali Radix, Bletillae Rhizoma and animal large intestine are the core components contributing to its detumescence and promoting granulation.

R285.5

甘肃省第三批陇原青年英才项目