目的 制备参柏（苦参Sophorae Flavescentis Radix-黄柏Phellodendri Chinensis Cortex）温敏凝胶（Shenbo thermosensitive gel，SBTG），对其进行质量评价并探究其对痔疮大鼠模型的药效作用。方法 以泊洛沙姆407（Poloxamer 407，P407）、泊洛沙姆188（Poloxamer 188，P188）为凝胶基质，以胶凝温度作为评价指标，采用Box-Beheken设计-响应面法（Box-Beheken design-response surface method，BBD-RSM）确定SBTG最优处方，并对其外观性状、微观形态、流变学特性、体外释药等进行评价。构建痔疮模型大鼠，以血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）、IL-1β及肛周肿胀度、直肠系数等为指标，考察SBTG治疗痔疮模型大鼠的药效。采用荧光定量PCR法、蛋白质印迹法（Western Blotting）检测直肠组织中缺氧诱导因子-1α（hypoxia-inducible factor-1α，HIF-1α）、血管内皮生长因子（vascular endothelial growth factor，VEGF）、基质金属蛋白酶-9（matrix metalloproteinase-9，MMP9）、组织金属蛋白酶抑制因子-1（tissue inhibitor of metalloproteinase-1，TIMP-1）的表达，探索其作用机制。结果 SBTG处方为P407用量15%，P188用量2.5%、聚山梨酯-80用量1.8%、1,2-丙二醇用量15%、参柏提取物用量5%；SBTG胶凝温度为33 ℃，室温下为棕黄色较为黏稠且具有流动性的液体，33 ℃及以上即转为棕黄色凝胶状半固体，微观形态为稳定的三维网状结构。体外释放结果表明，SBTG中指标成分（氧化苦参碱、苦参碱、小檗碱）释放时间较参柏提取物溶液长、具有缓释作用，符合一级动力学方程。药效学研究表明，与空白组相比，模型组大鼠肛门潮湿度增加且黏液溢出增多，偶见轻度糜烂，排泄物积滞带血；与模型组相比，阳性药（马应龙痔疮膏）组和SBTG组大鼠肛周肿胀程度明显降低，黏液分泌、糜烂、便秘及出血等症状得到明显改善；可抑制炎性细胞浸润，血清中炎性因子TNF-α、IL-6、IL-1β水平显著降低（P＜0.001）。SBTG可抑制HIF-1α、VEGF、MMP9表达，提高TIMP-1表达。结论 SBTG处方及制备工艺简单、可行性高，具有良好的缓释性能，且对痔疮模型大鼠表现出良好的治疗作用，可改善炎症反应及肛门直肠组织病理学损伤。

Objective Shenbo [Kushen (Sophorae Flavescentis Radix, SFR)-Huangbo (Phellodendri Chinensis Cortex, PCC)] thermosensitive gel (SBTG, 参柏温敏凝胶) was prepared to evaluate its quality and investigate its efficacy in a rat model of hemorrhoids. Methods Poloxamer 407 (P407) and Poloxamer 188 (P188) were used as gel matrices, and the gelation temperature was used as the evaluation index, and the Box-Beheken design-response surface method (BBD-RSM) to determine the optimal prescription of SBTG and evaluate its appearance properties, micromorphology, rheological properties and in vitro drug release. A hemorrhoid model rat was constructed, and the efficacy of SBTG in treating hemorrhoid model rats was investigated by using serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and the degree of perianal swelling and rectal coefficient as indicators. Fluorescence quantitative PCR and protein blotting (Western Blotting) were employed to detect hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) to explore their mechanisms of action. Results The prescription of SBTG was 15% P407, 2.5% P188, 1.8% polysorbate-80, 15% 1,2-propanediol, and 5% ginseng cypress extract; the gelation temperature of SBTG was 33 ℃, and it was a brownish-yellow viscous liquid with mobility at room temperature, and it transformed into a brownish-yellow gelatinous semi-solid at 33 ℃ or higher, and the microscopic morphology was the stable 3D reticulation structure. The microstructure is a stable three-dimensional mesh structure. The in vitro release results showed that the release time of the index components of SBTG (oxymatrine, matrine, berberine) was longer than that of the solution of SFR-PCC extract, and it had a delayed-release effect, which was in accordance with the first-degree kinetic equation. Pharmacodynamic studies showed that, compared with the blank group, the model group of rats increased anal wetness and mucus overflow, occasional mild erosion, excreta stagnation with blood; compared with the model group, the positive drug (Ma Yinglong Hemorrhoidal Ointment) group and the SBTG group of rats perianal swelling was significantly reduced, and symptoms such as mucus secretion, erosion, constipation and bleeding were significantly improved; it could inhibit inflammatory cell infiltration, and the serum inflammatory factors, TNF-α, IBT and PBTG, could also be used to treat the inflammation in rats. The levels of TNF-α, IL-6 and IL-1β were significantly reduced (P < 0.001). SBTG could inhibit the expression of HIF-1α, VEGF and MMP9, and increase the expression of TIMP-1. Conclusion SBTG prescription and preparation process is simple and feasible, has good slow-release performance, and shows good therapeutic effect on hemorrhoid model rats, which can improve the inflammatory response and anorectal histopathological damage.

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江西省重点研发计划（20224BBG71023）;江西省中医药标准化技术委员会标准化项目（2024A010）;江西中医药大学2023年“大学生创新创业训练计划”项目（X202310412176）;2023年度江西中医药大学校级研究生创新专项（JZYC23S68）;医院定向委托项目（2004-5252200403）