黄芩汤有效部位组方抗大鼠溃疡性结肠炎的实验研究

【作者】 丁晓刚；

【导师】 傅延龄；

【作者基本信息】 北京中医药大学 ， 中医临床基础， 2003， 博士

【摘要】 溃疡性结肠炎(Ulcerative Colitis, UC)是最严重的胃肠道疾病之一，近年来其发病率逐渐升高，病因及确切发病机制至今未明，一般认为涉及到遗传、免疫、感染、精神等多方面的因素。本病的临床表现具备炎症性肠病的特点，可见脓血便或粘液血便、里急后重，或伴腹痛、发热等症状。本病常突然起病，病情轻重悬殊，多数病程缓慢，有反复发作倾向，少数病例急性暴发，病情凶险。由于本病治愈难度大，且常易复发，并与结肠癌的发病存在一定的关系，因此被世界卫生组织列为现代难治病之一。西药在治疗本病上大多存在停药后易复发，长期用药副反应多，部分顽固性病例疗效并不理想等缺点。因此寻找更为有效、副作用少的药物成为当今的研究重点。中药在治疗溃疡性结肠炎方面有显著优势，具有较突出的开发研究价值和广阔的前景。 本研究在系统整理古今文献的基础上，结合导师的临床经验，以中药复方的有效成分研究思路为依托，就黄芩汤及其单味药有效部位组方对大鼠实验性溃疡性结肠炎的作用进行了药效学研究、拆方研究及疗效机制研究。 药效学研究结果表明，黄芩汤及其单味药有效部位组方都具有较好的抗炎、止泻、镇痛作用，并可改善UC大鼠的一般状况，对UC大鼠的病理组织学改变也有较好的修复作用。 拆方研究结果表明，黄芩汤单味药有效部位的各组方均有不同程度的抗炎、止泻、镇痛作用，其中以黄芩苷+甘草酸+白芍总甙十大枣cAMP组效果最佳。由此初步确认黄芩苷、甘草酸、白芍总甙，大枣cAMP是黄芩汤治疗溃疡性结肠炎的主要物质基础。 黄芩汤有效部位组方治疗UC大鼠作用机制的研究结果表明，UC大鼠的外周血IL-1β含量显著升高，进一步证实了 IL-1β在溃疡性结肠炎发展过程中的重要作用。IL-4具有下行调节作用，可抑制IL-1β产量，抑制超氧化物阴离子形成。本实验表明UC大鼠外周血IL-4含量显著降低，同时结肠组织中SOD的活力也降低，这在一定程度上加重了IL-1β等细胞因子的致炎作用和氧自由基对细胞的损伤，MDA含量的升高则证实了这一点。UC大鼠经黄芩汤有效部位组方治疗后，IL-1β和MDA含量降低，而IL-4和SOD含量升高，炎症损伤程度也有明显减轻。因此，黄芩汤有效部位组方对IL-1β、IL-4、SOD、MDA均有一定的调节作用，对UC大鼠的治疗是有效的，并从细胞因子和自由基角度说明了本方的作用机制，反映出中药多环节、多途径、多靶点的作用特点。更多还原

【Abstract】 Ulcerative colitis (UC) is one of the most serious gastrointestinal disease. Incidence of UC gradually increases with years. The etiological factor and pathogenesis remain unknown. The major factors generally include heredity, immune, infection and psychosomatic theory. The major symptoms of UC include diarrhea, rectal bleeding, the passage of mucus, tenesmus and abdominal pain, those symptoms is characteristic of inflammatory bowel disease. The onset of UC is acute and patient’s condition is great disparity. In general, UC’s progress is slow, but it tends to relapse. Severity condition of this disease may be found in some case who are acute. UC has been listed as refractory disease by WHO because it’s treatment is very difficulty and frequently relapse, meanwhile, it correlates with cancer of colon. There are some deficiencies of UC’s treatment through western medicine, such as frequently relapse after drug withdrawal, there are some side effect after taking medicine in a long time, there is no good effect in refractory case. So, it is the most important research to find effective drug. There are significant superiority, prominent investigation value and wide prospect in the aspect treatment of UC by Chinese medicine.This paper base on systemically arranging literature and tutor’s clinic experience, meanwhile, depend on the ways of thinking in the active elements of Chinese medicine research. Pharmacodynamics, taking prescription apart and curative mechanism that compound elements of HuangQinTang and HuangQin Tang treat experimental ulcerative colitis on rat were observed.Pharmacodynamics result show that compound elements of HuangQinTang and HuangQin Tang have good effect of anti-inflammatory, antidiarrhea and relieve pain, meanwhile, it can improve the general condition and histopathologic condition.Taking prescription apart result show that compound elements of HuangQinTang and HuangQin Tang have good effect of anti-inflammatory, antidiarrhea and relieve pain on some extent. The group of Baicalin + Glycyrrhizic acid + Panglycoside of white peony root + cAMP of jujube have the best effect in all group. So, the main substance that HuangQin Tang treat UC are Baicalin, Glycyrrhizic acid, Panglycoside of white peony root and cAMP of jujube.The curative mechanism that compound elements of HuangQinTang treat UC show that IL-1 , IL-4, SOD, MDA had significant difference between model group and normal group ( P < 0.01 ) .Meanwhile,the medium dosage group of compound elementsAbstractof HuangQinTang can significantly decrease the content of IL-1 , MDA and increase the content of IL-4, SOD,which significantly differs from those of the model group ( P更多还原