基于线粒体能量代谢探讨溃疡性结肠炎脾虚为本的病理基础

Ulcerative Colitis (UC) is the disease of no clear etiology and complex pathogenesis. Western medicine hasn't had any specific or targeted treatment for this disease with poor efficacy of contra-relapse, whereas Traditional Chinese Medicine (TCM) treatment has been very effective in recent years. The study is guided by the pathogenesis theory that spleen deficiency is the basis and dampness-heat and stagnant blood are the manifestation. The comprehensive treatment program of TCM showed its advantages in therapeutic effect. And spleen deficiency is considered to be the basis of UC recurrence. The study selects UC rats as research objectives according to the spleen-deficiency-rooted pathological basis and the spleen - the mitochondria-related theory. With the utilization of modern medical technology, the study will investigat the influence and adjustment mechanism of invigorating qi and strengthening the spleen therapy working on mitochondrial energy metabolism in accordance with its influence on mitochondria energy metabolism and immune injury, microcirculatory disturbance in the different UC periods. The study will clarify the effect of the mitochondrial energy metabolism abnormalities on the pathogenesis of UC, clear the relationship between mitochondrial energy metabolism abnormalities and spleen deficiency, and preliminarily will reveal the role of spleen deficiency in UC attack and recurrence and the material basis, with seeking for the recurrent pathological mechanism of UC and clearing the mechanism and application of laws of invigorating qi and strengthening the spleen therapy in the treatment process of UC which results in improving the clinical efficacy of UC contra-recurrence treatment.

溃疡性结肠炎（UC）病因不清，发病机制复杂，西医尚无特异性、针对性治疗手段，抗复发疗效不佳，近年来中医治疗取得良效。本课题组以"脾虚为本，湿热、瘀血为标"病机理论为指导，采用中医综合治疗方法显示了其疗效优势，脾虚被认为是UC复发的根本。本课题以UC大鼠为研究对象，围绕"脾虚是UC 发病之本"的病机，从"脾-线粒体相关"理论出发，利用现代医学技术，针对益气健脾法在UC不同时段对线粒体能量代谢与免疫损伤、微循环障碍的影响，探讨益气健脾法对线粒体能量代谢的影响及调节机制，阐明线粒体能量代谢异常在UC发病中的作用，明确线粒体能量代谢异常与脾虚的关系，初步揭示脾虚在UC发病和复发中的作用及物质基础，寻求UC反复发作的病理机制，明确益气健脾法在UC治疗过程中的作用机制和应用规律，从而提高UC抗复发治疗的临床疗效。

溃疡性结肠炎（Ulcerative Colitis，UC）是一种病因尚未明确的慢性疾病，以大肠（结肠与直肠）黏膜与黏膜下炎症为主要特征的病变。临床上以黏液脓血便、腹泻、腹痛和里急后重等为主要症状。该病反复发作，迁延日久，并与结肠癌的发病有一定关系，被世界卫生组织列为现代难治疾病。近年来，随着生活水平的提高，工作压力的增大，我国发病率逐年上升。UC发病机制复杂，目前西医尚无特异性、针对性治疗手段，抗复发疗效不佳。中医在整体观念与辨证论治指导下，辨病与辨证相结合治疗本病，近年来取得良效，尤其是在提高治愈率、降低复发率方面显现出独特的优势。UC病机被概括为脾虚为发病之本，湿热为致病之标，瘀血为局部病理变化，内疡为局部病理表现。在此病机理论指导下，将辨证和辨病相结合，采用分期、分阶段的中医序贯治疗方法。大量反复的临床实践证实这种中医序贯治疗方法疗效显著，复发率较前大大降低，远期疗效明显改善。这种序贯治疗方法之所以显示出疗效优势，是因为突破了以往单一治疗思路的局限，以中医的整体观念和辨证论治思想为指导，重视疾病发生发展的整体性和动态变化，分清主次，标本兼顾。尤其是在UC的治疗过程中，把握脾虚是发病和复发的根本，适时、恰当地运用了益气健脾法，成为提高临床疗效、降低复发率的关键。. 因此，本课题以UC大鼠为研究对象，围绕“脾虚是发病之本，湿热是致病之标”的病机，分析比较了UC急性期、慢性期不同时期的免疫损伤与炎性反应，观察了结肠黏膜线粒体结构改变与能量代谢的变化情况，探讨了线粒体异常与免疫损伤的相关性；比较了不同时期不同分组下的清热解毒方、益气健脾方、益气解毒方的疗效及其对线粒体与免疫损伤的影响。. 通过课题研究，取得了四项重要成果：①UC发病过程中线粒体结构和能量代谢异常呈现出与免疫损伤的不同步性；②UC慢性期病变持续存在，维持治疗可明显改善慢性期的病变程度；③中药序贯治疗方法显示出中医辨证论治的强大疗效优势；④UC脾虚的病理基础可能与线粒体结构损伤、能量代谢异常、抗炎与免疫抑制活性降低有关。本次研究发现，脾虚与UC免疫调控、线粒体功能等方面存在一定相关性，进一步研究有望揭示UC脾虚为本的物质基础，以期在此基础上找到UC反复发作病理机制的突破口。