溃疡性结肠炎（ulcerative colitis，UC）是一种反复发作的慢性非特异性炎症疾病。由于UC病因复杂，发病环节多，治愈难度大，复发率高，预后较差且增加患结肠癌的风险而被世界卫生组织列为现代难治疾病之一。UC临床常用的治疗方法是药物治疗，氨基水杨酸类和糖皮质激素类药物是UC活动期治疗的首选药物，免疫抑制剂通常用于重症难治性UC的治疗。近年来，UC治疗药物临床试验申请（IND）呈现上升趋势。非临床药效学试验是支持药物进入II期探索性临床试验的重要依据，而动物模型是非临床药效学研究的关键因素。目前UC非临床研究模型比较成熟，近年来随着转基因（transgenic，Tg）和基因敲除（knock out，KO）技术的发展，可以选择使用各种UC动物模型解决与UC相关的特定病理生理问题，并对特定成分/途径相关的候选药物进行非临床药效学评价。本文对目前UC非临床药效学模型种类、潜在的病理生理学基础进行综述，并根据各模型特点对其在新药研发中的应用提出一些建议，以期为UC药物非临床药效学评价以及UC治疗药物的研发提供参考。

Ulcerative colitis (UC) is an idiopathic chronic relapsing-remitting inflammatory disease. Owing to its etiological complexity, onset variability, curable difficulty, high recurrence rate, poor prognosis and increasing risk of colon cancer,UC has been listed as one of the most formidable diseases by the World Health Organization. Drug treatment is the conventional method for UC, aminosalicylates and glucocorticoids are the first choice to treat active UC. Immunosuppressants are mostly used in severe refractory UC. In recent years, the investigational new drug (IND) of UC therapeutic drugs has shown an upward trend. Nonclinical pharmacodynamic test is an important basis to support the entry of drugs into phase II exploratory clinical trial, and animal model is the key factor of nonclinical pharmacodynamic research. At present, the nonclinical research model of UC is relatively mature. In recent years, with the development of transgenic (Tg) and gene knockout (KO) technology, we can choose to use various UC animal models to solve specific pathophysiological problems related to UC, and evaluate the nonclinical pharmacodynamics of candidate drugs related to specific components/pathways. This paper reviews the types of nonclinical pharmacodynamic models and potential pathophysiological basis of UC, and puts forward some suggestions on their application in new drug research and development according to the characteristics of each model, in order to provide reference for the nonclinical pharmacodynamic evaluation of UC drugs and the research and development of UC therapeutic drugs.

R975