【作者】 朱飞叶；

【导师】 徐珊；

【作者基本信息】 浙江中医药大学 ， 中医内科学， 2014， 博士

【摘要】 目的：梳理中医对便秘的病因病机、治疗概况以及慢传输型便秘的发病机制和芍药甘草汤治疗的可能机制。芍药甘草汤是我们临床常用的治疗便秘的方剂,具有较好的临床疗效,为此需要明确其作用机理,以期提高中医对便秘的认识,为芍药甘草汤治疗慢传输型便秘提供实验依据,为进一步提高临床疗效打下基础。方法：1.文献研究：通过收集整理古代及现代文献,系统分析中西医对便秘的认识及芍药甘草汤的作用机制。2.实验研究：50只Wistar大鼠按体重根据随机数字表法分为5组：正常对照组、模型对照组、莫沙必利组、芍药甘草汤低剂量组、芍药甘草汤高剂量组。应用复方地芬诺酯灌胃制备慢传输型便秘的大鼠模型,各组连续给药14d后进行相应治疗,观察其粪便数量及含水率,结肠推进率,NO、NOS、VIP、P物质等肠神经递质的变化以及SCF/c-kit信号通路的改变。结果：1.文献研究：慢传输型便秘是一种功能性便秘,其发病机制与肠神经系统、消化道平滑肌、结肠内的Cajal间质细胞、自身免疫、心理因素等异常有关。中医认为,饮食不节,平素喜食辛辣厚味、煎炒酒食,而致胃肠积热；或忧郁思虑而致气机郁滞,日久化热伤阴,或熬夜劳累,煎熬阴液,致使阴津亏虚,导致便秘的发生。芍药甘草汤柔肝理脾、养阴生津,与病机相对应。2.实验研究：芍药甘草汤可以改善慢传输型便秘大鼠粪便性状,增加粪便数量,提高粪便含水率(P<0.05)；促进结肠推进功能(P<0.01)；减少抑制性神经递质NO、NOS和VIP的表达(P<0.05),对P物质含量有一定程度提高,但差异无统计学意义(P>0.05)；提高c-kit蛋白及mRNA的表达(P<0.05),从而增加ICC的数量和功能,进而加快结肠运动,并增加结肠的分泌,提高粪便的含水量；能增加SCF蛋白表达；并一定程度增加SCF mRNA及PI3K mRNA的表达,但差异无统计学意义(P>0.05)。结论：芍药甘草汤可以提高结肠推进率、粪便含水率及粪便数量,改善便秘症状,并且通过降低抑制性神经递质NO、NOS、VIP,提高肠道平滑肌的运动；通过调控SCF/c-kit信号通路增加ICC数量,改善结肠的慢波的产生,调控平滑肌收缩的节律；芍药甘草汤还可以增加结肠的分泌,提高粪便含水率,从而发挥治疗慢传输型便秘的作用。芍药甘草汤柔肝理脾、养阴生津适合于慢传输型便秘的治疗。更多还原

【Abstract】 Objective To summarize the etiology, pathogenesis and treatment of constipation in TCM, pathogenesis of slow transit constipation and possible mechanisms of Shaoyao Gancao Decoction. Shaoyao Gancao Decoction is our commonly used prescription in the treatment of constipation, which has good efficacy. Therefore, it is important to research the mechanism of Shaoyao Gancao Decoction for improving the knowledge of constipation in TCM, providing experimental evidence for Shaoyao Gancao Decoction in the treatment of slow transit constipation and laying the foundation to further improve the clinical efficacy.Methods1. Literature research:by collecting ancient and contemporary literature, systematic and comprehensive analysis the understanding of constipation and the mechanism of Shaoyao Gancao Decoction in Chinese and Western medicine.2. Experimental study:50Wistar rats were randomly divided into five groups:normal control group, model group, mosapride group, Shaoyao Gancao Decoction low-dose group (SGD-LG), Shaoyao Gancao Decoction high dose group (SGD-HG). Application of compound diphenoxylate in gavage for14d for slow transit constipation rats model and then treated with above drugs, to observe the changes of the volume and moisture content of fecal, neurotransmitter (NO, NOS, VIP, P substances) and SCF/c-kit signaling pathway.Results1. Literature research:Slow transit constipation is a functional constipation, its pathogenesis was related to the enteric nervous system, gastrointestinal smooth muscle, Cajal interstitial cells in colon and autoimmune. It is believed in Chinese medicine that eat too much, like to eat spicy greasy and fry food and wine, will lead to gastrointestinal accumulated heat; thinking too much and depression lead to qi stagnation, which will transform to heat and injury Yin; burning the midnight oil damage Yin, resulting Yin deficiency, all of which will lead to constipation. Shaoyao Gancao Decoction with nourishing liver, regulating spleen, nourishing Yin and promoting the production of body fluid correspond to pathogenesis.2. Experimental study:Shaoyao Gancao Decoction can improve stool quantity and moisture content of slow transit constipation rat(P<0.05); promote colonic propulsion function (P <0.01); reduce the inhibitory neurotransmitter NO, NOS and VIP expression(P<0.05); improve substance P to some extent, but the difference was not statistically significant (P>0.05); increase the expression of c-kit protein and mRNA(P<0.05); thereby increase the number and function of ICC, accelerate the movement of the colon and increase the secretion of it to moisture the stool; increase the expression of SCF protein; to some extent increase the expression of SCF mRNA and PI3K mRNA, but the difference was not statistically significant(P>0.05).Conclusion Shaoyao Gancao Decoction can improve colon advance rate, fecal water content, the number of stool, and constipation symptoms. It can promote intestinal smooth muscle sport by reducing the inhibitory neurotransmitter NO, NOS and VIP. It can increase the number of ICC, improve colon slow wave, regulate of smooth muscle contraction rhythm by regulating SCF/c-kit signaling pathway. Shaoyao Gancao Decoction can also improve fecal moisture content by increasing the secretion of the colon, and thus play a role in the treatment of slow transit constipation. Shaoyao Gancao Decoction with nourishing liver, regulating spleen, nourishing Yin and promoting the production of body fluid is suitable for slow transit constipation treatment.更多还原