潰瘍性結(jié)腸炎（ulcerative colitis，UC）是一種反復(fù)發(fā)作的慢性非特異性炎癥疾病。由于UC病因復(fù)雜，發(fā)病環(huán)節(jié)多，治愈難度大，復(fù)發(fā)率高，預(yù)后較差且增加患結(jié)腸癌的風(fēng)險而被世界衛(wèi)生組織列為現(xiàn)代難治疾病之一。UC臨床常用的治療方法是藥物治療，氨基水楊酸類和糖皮質(zhì)激素類藥物是UC活動期治療的首選藥物，免疫抑制劑通常用于重癥難治性UC的治療。近年來，UC治療藥物臨床試驗申請（IND）呈現(xiàn)上升趨勢。非臨床藥效學(xué)試驗是支持藥物進(jìn)入II期探索性臨床試驗的重要依據(jù)，而動物模型是非臨床藥效學(xué)研究的關(guān)鍵因素。目前UC非臨床研究模型比較成熟，近年來隨著轉(zhuǎn)基因（transgenic，Tg）和基因敲除（knock out，KO）技術(shù)的發(fā)展，可以選擇使用各種UC動物模型解決與UC相關(guān)的特定病理生理問題，并對特定成分/途徑相關(guān)的候選藥物進(jìn)行非臨床藥效學(xué)評價。本文對目前UC非臨床藥效學(xué)模型種類、潛在的病理生理學(xué)基礎(chǔ)進(jìn)行綜述，并根據(jù)各模型特點(diǎn)對其在新藥研發(fā)中的應(yīng)用提出一些建議，以期為UC藥物非臨床藥效學(xué)評價以及UC治療藥物的研發(fā)提供參考。

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