目的 制备三乌胶提取物水凝胶并进行表征及考察其对类风湿性关节炎的治疗作用。方法 采用Franz池法考察三乌胶提取物中二苯乙烯苷、苯甲酰新乌头碱、8-去乙酰滇乌碱、去乙酰粗茎乌头碱甲、草乌甲素和大黄素的体外渗透效果，制备出三乌胶提取物水凝胶并对其理化性质进行表征；同时，建立胶原诱导的类风湿性关节炎（collagen-induced rheumatoid arthritis，CIA）大鼠模型，研究经皮递送模式下三乌胶提取物对类风湿性关节炎的治疗作用。结果 制备的三乌胶提取物水凝胶在常规情况下始终保持凝胶状态；并且其三维交联网状结构可使药物更好的持续性地释放，从而达到缓释效果。体内药理实验表明，三乌胶提取物水凝胶显著降低CIA大鼠的足厚度、足体积、关节炎指数水平和血清中类风湿因子（rheumatoid factor，RF）、C反应蛋白（C-reactive protein，CRP）和B细胞淋巴瘤因子-2（B-cell lymphoma-2，Bcl-2）的水平及升高Bcl-2相关X蛋白（Bcl-2-associated X protein，Bax）水平；与口服相比，水凝胶能降低谷氨酸转氨酶（aspartate aminotransferase，AST）、丙氨酸转氨酶（alanine aminotransferase，ALT）、肌酐和尿素氮水平和脏器病变程度。结论 采用经皮递送的局部给药模式，三乌胶提取物在保留治疗作用的同时降低了由于口服给药引起的脏器毒性，为今后三乌胶提取物外用制剂的研究提供了可能性。

Objective To prepare and characterize Sanwujiao extract-hydrogel and investigate its therapeutic activity on rheumatoid arthritis.Methods Franz cell method was used to investigate the in vitro permeation effects of 2,3,5,4'-tetrahydroxy stilbene 2-Ο-β-D-glucoside, benzoylmesaconine, 8-deacetylyunaconitine, sinapic acid crassicauline, crassicauline A and emodin in the Sanwujiao extract. The Sanwujiao extract-hydrogel was prepared and its physical and chemical properties were characterized; At the same time, the CIA rat model was established to study the therapeutic activity of Sanwujiao extract on rheumatoid arthritis under percutaneous delivery mode. Results The Sanwujiao extract-hydrogel was always in the state of gel under normal conditions; And its three-dimensional cross-linked network structure can make the drug release better and continuously, so as to achieve the sustained-release effect. In vivo pharmacological tests showed that the Sanwujiao extract-hydrogel significantly decreased the foot thickness, foot volume, arthritis index level, RF, CRP and Bcl-2 levels in serum and increased Bax levels in CIA rats; It can also reduce the levels of AST, ALT, creatinine and blood urea nitrogen and the degree of organ lesions. Conclusion Using the local delivery mode of percutaneous delivery, Sanwujiao extract can retain the therapeutic activity and reduce the organ toxicity caused by oral administration, which provides the possibility for the study of external preparations of Sanwujiao extract in the future.

R283.6

国家重大科技专项(202002AA100004-2);国家重大科技专项(202102AA310045);国家重大科技专项(202002AA1000056)