溃结安对异常胆液质型UC病证载体模型大鼠NEI网络功能的整体调控及其机制

Functional disorder of nervous - endocrine - immune(NEI) network is closely related to the occurrence of ulcerative colitis. Uygur Traditional Medicine believes that the abnormal safra induced ulcerative colitis. We found that the role of Uygur medicine kuijiean（KJA） treatment of ulcerative colitis in rats is mainly related to a variety of gene expression that related to immunity, metabolism, cell signal transmission . This investigation is to establish abnormal safra disease Rat model and used for the treatment with KJA . HPA axis, colon tissue, serum and urine as the object of study, carry on transcriptional genomics and metabolomics research. First, investigate whether abnormal safra affects the rats to the susceptibility to UC. Second, filter abnormal safra hilit and the role of KJA-related structural genes, metabolic component, draw the structure of gene expression, metabolic differences in spectrum and network control mode .Third, Metabolomics research on the serum, urine, and colon tissue of the abnormal safra and abnormal belhem type UC patients before and after KJA intervention to further validate the results of animal experiments. Finlay, to detect of serum ACTH and CORT, IL-1,IL-6,IL-10. Through the combination of Western Medicine and Uygur Traditional Medicine, and combining the overall and partial, Discusses the overall control function of KJA to NEI network of abnormal safra disease rat model and it's mechanism.

溃疡性结肠炎（UC）的发生与神经-内分泌-免疫（NEI）网络功能紊乱密切相关，维医认为异常胆液质旺盛诱发UC的发生，研究发现维药溃结安（KJA）治疗大鼠UC的作用主要与免疫、代谢、细胞间信号传递相关的多种基因表达有关，但缺乏整体水平的研究。本研究拟建立异常胆液质证、异常胆液质病证UC大鼠模型，进行KJA干预，以HPA轴、结肠组织、血清及尿液等作为研究对象，进行形态学、转录组学和代谢组学研究：1、探讨异常胆液质证是否影响大鼠对UC的易感性2、筛选与KJA的作用和异常胆液质病证相关的结构基因、代谢组分，绘制结构基因表达、代谢差异谱和网络式调控模式图3、对异常胆液质和粘液质型UC患者KJA干预前后的结肠组织、血清、尿液进行代谢组学研究4、检测血清中ACTH、CORT、IL 1等指标。通过西医与维医、整体与局部的结合，探讨KJA对异常胆液质证、异常胆液质病证大鼠NEI网络功能的整体调控及其机制。

本课题本研究拟建立异常胆液质证、异常胆液质病证 UC 大鼠模型，进行 KJA 干预，以 HPA 轴、结肠组织、血清作为研究对象，进行形态学、转录组学和代谢组学研究：1、首次发现异常胆液质体液的形成与神经内分泌免疫网络紊乱有关，其中甲状腺激素含量降低是异常胆液质证形成中的关键因素。2、通过研究发现甲状腺激素含量降低是异常胆液质证与UC形成的共同物质基础，甲状腺激素含量降低使结肠出现能量失衡、氧化损伤和细胞膜稳定性破坏，是异常胆液质证与UC 结肠中出现的共同结果，这一结果也是造成异常胆液质证更易诱发UC的原因之一，为异常胆液质证诱发UC这一理论提供了实验依据。3、通过代谢组学及转录组学研究结果，绘制出异常胆液质及UC发生相关的代谢差异谱和网络式调控模式图 4、通过研究发现异常胆液质证模型的建立方法较好的模拟了UC致病因素中环境、饮食、精神因素的作用。可为今后建立更符合人类UC临床表现的动物模型提供参考。5、溃结安药物干预后，关键基因的表达发生逆转，初步确立溃结安治疗溃疡性结肠炎的分子机制。