肠愈宁颗粒对溃疡性结肠炎大鼠JAK/STAT通路影响的拆方研究

Ulcerative colitis (UC) is inflammatory bowel disease. The exact cause of inflammatory bowel disease has not yet entirely clear, therefore, for the cause of ulcerative colitis to implement effective prevention and treatment, the treatment of inflammatory bowel disease can provide an important basis . After 20 years of our clinical and experimental studies，we have found that the active key of UC is the actual situation of the pathogenesis leading to persistent disease and miscellaneous complex, relying on spleen hypofunction accompanied by dampness accumulation. We summed up the therapy that to fortify the spleen dry dampness and clearing away toxic material in treating UC. After years of exploration experience, summed up the more granules of intestinal side, in terms of symptoms and pathology, and achieved remarkable results. The key issue in the previous study, based on a Real Time PCR technique and Western blot, the more granules of intestinal side after demolition of "spleen", "dampness", "detoxification" of the law and its combination of IL-6, JAK2, STAT1, STAT3, SOCS1, SOCS3 gene and protein expression. The research topics of research will clarify the intestine more granules and its Ingredients on ulcerative colitis JAK / STAT pathway and its negative regulator of the role and impact of the intervention and after the party split to reveal the synergy between the various methods of UC effective blocking and treatment, and provide a scientific basis.

溃疡性结肠炎（UC）属炎症性肠病，炎症性肠病的确切病因至今尚未完全明确，因此，针对溃疡性结肠炎病因实施有效的防治，能为炎症性肠病的治疗提供重要的依据。我们经过20余年的临床和实验研究发现，UC活动期的病机关键是虚实兼杂致使病情迁延复杂，脾虚挟湿毒而致。在治疗方法中总结出健脾燥湿解毒法治疗本病，并经过多年摸索总结出经验方肠愈宁颗粒，无论从症状及病理上，取得了显著的疗效。本项课题在既往研究基础上，采用Real Time PCR技术和免疫印迹技术，研究肠愈宁颗粒拆方后"健脾"、"燥湿"、"解毒"各法及其组合对IL-6、JAK2、STAT1、STAT3、SOCS1、SOCS3的基因和蛋白表达的影响。本项课题的研究成果将阐明肠愈宁颗粒及其拆方对溃疡性结肠炎JAK/STAT通路及其负调控因子的干预作用和影响，并揭示拆方后各法之间的协同作用，对UC进行有效的阻断和治疗，并提供科学的理论依据。

实验成功复制了改良复合法诱导的活动期UC大鼠模型，实验结束后，检测结果显示，（1）模型组IL-6表达水平与空白组比较明显增高，各治疗组与模型组比较，表达下调，差异有统计学意义（P＜0.05）；健脾燥湿解毒组、西药组分别与健脾组、燥湿组、解毒组、健脾燥湿组、健脾解毒组、燥湿解毒组比较，IL-6表达下调明显，差异有统计学意义（P＜0.05），但二者之间无显著差异（P＞0.05）；（2）模型组结肠粘膜JAK2蛋白表达水平与空白组比较明显增高，各治疗组与模型组比较JAK2蛋白表达下调，差异有统计学意义（P＜0.05）；健脾燥湿解毒组、西药组分别与健脾组、燥湿组、解毒组、健脾燥湿组、健脾解毒组、燥湿解毒组比较，JAK2蛋白表达下调明显，差异有统计学意义（P＜0.05），但两者之间比较无显著差异（P＞0.05）；（3）模型组结肠粘膜STAT3蛋白表达水平与空白组比较明显增高；各治疗组与模型组比较STAT3蛋白表达下调，差异有统计学意义（P＜0.05）；各治疗组中以健脾燥湿解毒组STAT3蛋白下调最显著，差异有统计学意义（P＜0.05）；（4）模型组SOCS3表达水平与空白组比较明显下调，各治疗组与模型组比较，表达增高，差异有统计学意义（P＜0.05）；健脾燥湿解毒组、西药组分别与健脾组、燥湿组、解毒组、健脾燥湿组、健脾解毒组、燥湿解毒组比较，SOCS3表达增高明显，差异有统计学意义（P＜0.05），但二者之间无显著差异（P＞0.05）。. 其中大鼠模型血清中IL-6及结肠粘膜中JAK2、STAT3蛋白在溃疡性结肠炎活动期处于高表达，SOCS3处于低表达，且相互之间存在着相关关系，提示JAK/STAT信号传导通路关键分子表达异常可能是溃疡性结肠炎发病的重要机制。以健脾燥湿解毒法为原则创立的肠愈宁颗粒对活动期溃疡性结肠炎有治疗作用，能明显改善大鼠结肠粘膜病理状况。肠愈宁颗粒通过调控JAK/STAT细胞信号传导通路，降低活动期溃疡性结肠炎大鼠血清IL-6及结肠粘膜JAK2、STAT3蛋白的表达水平，增高SOCS3的表达水平，这可能是其治疗溃疡性结肠炎的主要机制之一。. 同时发表国内核心期刊论文3篇。