放射性直肠炎是盆腹腔肿瘤放疗常见的并发症，约30%患者因此中断放疗而影响预后，目前缺乏特效治疗药物及方法，西医多采用消炎、止血及对症治疗，疗效不佳，中医药有一定优势，多见于小样本临床观察，疗效不满意，因此迫切需要研发特效治疗药物。前期研究发现肠瑞灌肠剂通过下调IL-1βmRNA、NF-κB表达而减轻炎症反应，并通过上调6-Kote-PGF1α水平、下调TXB2水平而改善局部微循环，从而发挥治疗作用，该药获得新药发明专利，并成果转让、进入II期临床试验。本项目在此基础上，提出炎症诱导血管新生假说，观察肠瑞灌肠剂是否对血管新生具有抑制作用？应用AQP1基因敲除小鼠，研究AQP1是否参与放射性直肠炎的血管新生？应用免疫组化、PCR、Western Blot等技术阐明肠瑞灌肠剂调控NF-kB、AQP1相关信号通路发挥治疗放射性直肠炎的分子机制，为发现新药物、新靶点、创新发病机制提供实验依据。

The patients of abdominal and pelvic tumors treated by radiation therapy are often campanied with radiation proctitis, and about 30% patients diagnosed with radiation proctitis have to give up radiation therapy. Radiation proctitis seriously affects the prognosis of these patients. No effective drug or treatment is currently available. The western medicine treatments with anti-inflammatory and hemostatic for radiation proctitis are less effective. The traditional Chinese medicine treatments has been demonstrated to be less effective in some clinical observations of small samples. Therefore there is an urgent need for some novel drugs which have specially good effects on radiation proctitis. We have studied the treatment effect of Changrui enema in radiation proctitis rat mode. Exciting, we found Changrui enema reduced inflammation by inhibiting the expression of IL-1 β mRNA and NF- κB, and improved local microcirculation by up-regulating the level of 6-Kote-PGF1 α and down-regulating the level of TXB2. We have gained the new drug patent of Changrui enema, and have transfered the patent to pharmaceutical campany. The phase II trial of Changrui enema has been carried out recently. We propose the hypothesis that inflammation maybe induce angiogenesis in radiation proctitis. The purpose of this study is to evaluate Changrui enema treatment effect on AQP1 mediated induction angiogenesis in radiation proctitis by using AQP1 gene knockout mice, and to demonstrate the hypothesis molecular mechanism related with NF-κB and AQP1 signaling pathways by immunohistochemical technique, PCR and Western Blot. This study will discover novel treatment of traditional Chinese medicine, find new therapeutic targets, and develop pathogenic mechanisms of radiation proctitis.