【作者】 陈萌；

【导师】 王庆国；

【作者基本信息】 北京中医药大学 ， 中医临床基础·伤寒论， 2003， 博士

【摘要】 半夏泻心汤是临床中常用的、具有和解作用的经方之一，由辛温的半夏、干姜，苦寒的黄连、黄芩，甘补的党参、大枣、甘草组成。该方和胃降逆，开结除痞的功能受到了历代医家的公认，被用于许多脾胃疾病的治疗。心下痞是半夏泻心汤证的主要证候。从现代医学角度看，心下痞是由胃运动障碍所致。本课题组的成员针对半夏泻心汤的适应证，先后进行了该方的系列研究，其中包括调节胃肠功能的初步研究。实验结果显示，半夏泻心汤证与胃肠运动功能紊乱，特别是胃肠动力减弱具有很强的相关性。在此基础上，本课题进行了半夏泻心汤调节胃电节律的拆方研究。论文共分三部分：第一部分系统综述了半夏泻心汤的临床与实验研究概况，以及与其相关的胃节律紊乱综合征（GDS）和Cajal间质细胞（ICC）的研究进展。半夏泻心汤的应用涉及临床各科及人体各大系统，尤多用于各种消化系统疾病的治疗。其中，又以虚实并见、寒热错杂所致的急慢性胃炎、肠炎、消化道溃疡等胃肠道疾病最为合拍。有关的临床报道虽然很多，但仍以经验总结为主，作用机制研究较为缺乏。半夏泻心汤的实验研究日趋深化，在汤证实质、作用机理、配伍机理及毒理研究等方面取得了大量的研究成果，有望更有效地指导临床应用。半夏泻心汤证的主要临床表现为自觉胃脘部满闷不通，伴见恶心呕吐或肠鸣下利等。从症状学上看，心下痞与现代医学的GDS有非常密切的关系。GDS的主要症状包括恶心和（或）呕吐、上腹饱胀或疼痛、食欲不振、早期饱食感等一组症候群。临床上凡是有明显胃病临床症状的患者，具有胃功能性和（或）器质性疾病，以及其它能够导致胃节律紊乱的全身性疾病，胃电图（EGG）检查有各种胃电节律异常，即可诊断为GDS。其发病多与神经体液调节障碍、胃壁局部组织病理改变等有关，临床上常将其分为胃动过速、胃动过缓、胃节律失常三型。ICC可能是胃肠道慢波的起搏者，参与了慢波的传导，同时也是胃肠神经与平滑肌细胞联系的重要通道，参与了胃肠神经信息传递过程，在胃肠动力的调控中起着重要作用，与某些胃肠动力性疾病的发病有关。当前的研究包括ICC的命名与分类、识别方法、形态学与超微结构、在胃肠中的分布与发育、功能及相关疾病等。研究ICC对正确理解半夏泻心汤的胃肠动力学机制和临床药理学研究具有重要的意义。第二部分系统探讨了气论从进入哲学到仲景医学气论形成的发展历程、经方方元的研究意义、半夏泻心汤类方的方证。胃的气机升降失常是半夏泻心汤证形成的中心环节。为了对这种病理机制有一个全面的认识，分析仲景医学气论的内涵是十分必要的。有鉴于此，本文从追溯气论进入哲学开始，探讨了哲学气论经老庄、黄老道家、西汉新儒家到王充、张衡，医学气论经《黄帝内经》到张仲景的发展历程，初步总结了仲景医学气论的框架，并以其诠释仲景对于人体的生理、病理，疾病的诊断、治疗的认识，希望能对中医理论的廓清和现代化有所裨益。<WP=6>半夏泻心汤由辛温、苦寒、甘补三组药物组成。从方剂的演变规律来看，方中的半夏、干姜即具有温中下气作用的半夏干姜散；黄芩、黄连类似于具有清热消痞作用的大黄黄连泻心汤；人参、甘草、大枣类似于具有补脾作用的甘麦大枣汤。有鉴于此，本文将构成经方的有规律可循的最小方剂单元称为“经方方元”，在择要罗列的基础上分析了其特色，并提出了经方方元的研究思路。在《伤寒》和《金匮》中，仲景虽然提及了半夏泻心汤及其类方的方证，但对其形成机制和理法方药并未全面论述。有鉴于此，本文引入了《辅行诀》、《内经》、《本经》、《别录》等与仲景时代接近的古典医籍中的相关论述，以期还原仲景对半夏泻心汤类方方证的认识。第三部分的实验设计结合了方剂的演变规律和现代数理统计学方法，将半夏泻心汤拆为辛温、苦寒、甘补三组，并将这三个单味组作为三个不同的因素，采用23析因实验设计，选用大鼠胃电节律失常模型，观察了半夏泻心汤及其拆方各组对于胃电节律失常大鼠的胃电慢波频率变异系数、胃肌间神经丛c-kit阳性ICC含量、胃壁c-kit和SCF基因mRNA表达水平、血清SCF水平的调节作用，并根据实验结果分析了方中各单味组的药效及配伍特点，部分揭示了半夏泻心汤的消痞散结机制。其详细内容如下：半夏泻心汤及其拆方各组均具有不同程度的纠正胃电节律失常、调节胃肌间神经丛c-kit阳性ICC含量、抑制c-kit和SCF基因mRNA的表达水平的作用。辛苦组纠正胃电节律失常的作用在各给药组中最强。组成辛苦组的两个单味组是半夏泻心汤中一对药性相反的方元，分别具有温中下气和清热消痞的作用。因此，辛苦组尤其适用于胃中寒热错杂，气机升降失常所致的痞证。提示这种胃电节律失常有寒热错杂，气机逆乱的病机特点。各单味组在全方配伍中均起主要作用，以甘味组纠正胃电节律失常的作用最强，它虽弱于辛苦组和全方组，但与后两者并无显著性差异。提示造成这种胃电节律失常的原因是多方面的。辛苦组调节胃肌间神经丛c-kit阳性ICC含量的作用在各给药组中最强，推测仍与辛苦组寒热并调的作用有关。各单味组在全方配伍中均起主要作用，以苦味组的调节作用最强；各给药组之更多还原

【Abstract】 Banxiaxiexin decoction (BD), which has harmony-effect, is one of the classical prescriptions being widely used in clinic, especially in the treatment of digestive system disease. The pungent tasted pinellia, dried ginger, bitter tasted coptis, scutellariac, and sweet tasted asiabell, Chinese date, licorice composes it.Epigastric fullness is the major syndrome that is fitted BD; it is caused by the disorder of stomach movement. Aimed at the proper syndromes of BD, the stuff of this topic have done series of studies include the primary researches of the regulating effects of BD on gastrointestinal tract. The results show that the syndrome, which fitted BD, has great relativity with the reduced power of the stomach and intestine.Currently researches show that the constriction of gastric antrum disappeared when the slow wave out of gear, and interstitial cell of Cajal (ICC) plays a very important role in the process of Gastrointestinal dynamic adjustment. So, we suspected that there might be a closed relationship between the forming of the syndrome of epigastric fullness and the disorder of gastric rhythm mediated by ICC.Based on the knowledge we just mentioned above, we carried out the study on BD regulating gastric electric rhythm by divided design. The paper conclude three parts:In the first part, we reviewed the literatures of clinical and experimental studies on BD, and relative researches on Gastric Dysrhythmia Syndrome (GDS) and ICC.BD widely is used in clinic to treat many diseases of human (especially digestive system diseases). Experimental researches covered many sectors, such as mechanism of the compatibility, toxicological studies, etc. And a great deal of achievements has been gained.In semiology, epigastric fullness is very similar to GDS. The major symptoms of GDS include nausea, emesis, epigastric pain, anorexia, etc. All the symptoms mentioned above are familiar in many gastric functional diseases. In clinic, GDS can be divided into three kinds.ICC, the pacemaker of Gastrointestinal tract, which can promote the spread of electric activity, plays a very important role in the process of Gastrointestinal dynamic adjustment, has closed relationship with many gastric functional diseases. So, to study ICC is very important in understanding the mechanism of BD regulating gastrointestinal movement correctly.In the second part, we discussed Qi-theory, Jingfangfangyuan (the minimal unit of Zhangzhongjing’s prescription), prescription & syndrome of BD. <WP=9>In short, Qi-theory is rooted in Chinese ancient philosophy and the forming of syndrome fitted BD has closed relativity with Qi in the TCM. The three groups of herbs, which composed BD, can be considered as three Jingfangfangyuan. There are related descriptions on the prescription & syndrome of BD in classical medical works, such as The Yellow Emperor’s Canon of Internal Medicine, The legendary god of farming’s Canon of materia medica, etc.In the third part, we combined modern mathematical statistic methods and recipe evolvement rule , adopted 23 factorial experimental design , divided BD into three single-tasted drug groups (the group containing herbs pungent in flavor, the group containing herbs bitter in flavor, the group containing herbs sweet in flavor), chose animal model of gastric electric rhythm disorder, observed the effect of BD and each decomposed group (BD&EDG) in regulating animal model’s coefficient of variation of slow wave frequency of gastric electric rhythm, the content of c-kit＾│ ICC in stomach myenteric nerve plexus, the mRNA expression lever of c-kit and SCF gene in omni-wall of stomach, the lever of serum SCF. The results of this study are as follows:BD&EDG all have effects on rectifying the disorder of gastric electric rhythm, regulating c-kit＾│ ICC content in stomach myenteric nerve plexus, suppressing c-kit and SCF gene expression in omni-wall of stomach to various degrees. And there are significant difference between the treatment groups and the model group. Among all the treatment groups,更多还原