芍药甘草汤对慢传输型便秘大鼠的作用及其对肠神经递质及SCF/c-kit信号途径的作用机制研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
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。
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.
引文
1 杨向东,贺百林,贾英田.慢传输型便秘机理的研究近况[J].结直肠肛门外科,2011,17(4):264-267
    2 Stessman M. Bio feedback:its role in the treatment of chronic constipation [J]. Gastroenterol Nurs,2003,26(6):251-260
    3 方秀才,柯美云,罗金燕,等.中国慢性便秘的诊治指南(2007,扬州)[J].中华消化杂志,2007,27(9):619-622
    4 陈灏珠,林果为,王吉耀.实用内科学.北京:人民卫生出版社.2013,1913
    5 DouglasA.Drossman罗马Ⅲ功能性胃肠病.北京:科学出版社.2008,456
    6 杨向东,杨玉刚.便秘导致精神心理障碍的探讨[J].中国肛肠病杂志,2009,30(z1):142-145
    7 Rao S S C, Seaton K, Miller M J, et al. Psychological profiles and quality of life differ between patients with dyssynergia and those with slow transit constipation[J]. Journal of psychosomatic research,2007,63(4):441-449
    8 Dykes S, Smilgin-Humphreys S, Bass C. Chronic idiopathic constipation:a psychological enquiry[J]. European journal of gastroenterology & hepatology,2001,13(1):39-44
    9 王玉明,王邦茂,张维铭,等.功能性便秘与功能性腹泻病人5-羟色胺转运体基因多态性分析[J].中华消化杂志,2005,24(8):493-494
    10 Kim H J, Camilleri M, Carlson P J, et al. Association of distinct a2 adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders[J]. Gut,2004,53(6):829-837
    11 Sandler R S, Drossman D A. Bowel habits in young adults not seeking health care[J]. Digestive diseases and sciences,1987,32(8):841-845
    12 Drossman D A, Sandler R S, McKee D C, et al. Bowel patterns among subjects not seeking health care[J]. Gastroenterology,1982,83(3):1
    13 Rendtorff R C, Kashgarian M. Stool patterns of healthy adult males[J]. Diseases of the Colon & Rectum,1967,10(3):222-228
    14 Everhart J E, Go V L W, Johannes R S, et al. A longitudinal survey of self-reported bowel habits in the United States[J]. Digestive diseases and sciences,1989,34(8):1153-1162
    15 Evans R C, Kamm M A, Hinton J M, et al. The normal range and a simple diagram for recording whole gut transit time[J]. International journal of colorectal disease,1992,7(1): 15-17
    16 郭晓峰,柯美云,潘国宗,等.北京地区成人慢性便秘整群,分层,随机流行病学调查及其相关因素分析[J].中华消化杂志,2002,22(10):637-638
    17 沈峰,周惠清,陈光榆,等.上海市社区成年居民功能性便秘的流行病学调查[J].中华流行病学杂志,2012,33(3):296-300.
    18 左振魁,韩佳瑞.郑州市区居民便秘流行病学调查[J].中国肛肠病杂志,2012,32(6):50-52
    19 Pare P, Ferrazzi S, Thompson W G, et al. An epidemiological survey of constipation in Canada:definitions, rates, demographics, and predictors of health care seeking[J]. The American journal of gastroenterology,2001,96(11):3130-3137
    20熊理守,陈曼湖,陈惠新.广东省社区人群慢性便秘的流行病学研究[J].中华消化杂志,2004,24(8):488-491
    21 Tomita R, Fujisaki S, Ikeda T, et al. Role of nitric oxide in the colon of patients with slow-transit constipation[J]. Diseases of the colon & rectum,2002,45(5):593-600
    22 Tzavella K, Riepl R L, Klauser A G, et al. Decreased substance P levels in rectal biopsies from patients with slow transit constipation[J]. European journal of gastroenterology & hepatology,1996,8(12):1207-1211
    23 Tomita R Regulation of the peptidergic nerves (substance P and vasoactive intestinal peptide) in the colon of women patients with slow transit constipation:an in vitro study[J]. Hepato-gastroenterology,2007,55(82-83):500-507
    24 童卫东,张胜本.一氧化氮合酶,P物质在慢传输型便秘结肠壁内的异常表达[J].第三军医大学学报,1999,21(9):645-647
    25 Slater B J, Varma J S, Gillespie J I. Abnormalities in the contractile properties of colonic smooth muscle in idiopathic slow transit constipation[J]. British journal of surgery,1997, 84(2):181-184
    26 Knowles C H, Nickols C D, Scott S M, et al. Smooth muscle inclusion bodies in slow transit constipation[J]. The Journal of pathology,2001,193(3):390-397
    27 Dickens E J, Edwards F R, Hirst G D S. Selective knockout of intramuscular interstitial cells reveals their role in the generation of slow waves in mouse stomach[J]. The Journal of physiology,2001,531(3):827-833
    28 Lee J I, Park H, Kamm M A, et al. Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon[J]. Journal of gastroenterology and hepatology,2005,20(8):1292-1298
    29 Wedel T, Spiegler J, Soellner S, et al. Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon[J]. Gastroenterology,2002, 123(5):1459-1467
    30 He C L, Burgart L, Wang L, et al. Decreased interstitial cell of Cajal volume in patients with slow-transit constipation[J]. Gastroenterology,2000,118(1):14-21
    31 童卫东,李朝阳,刘宝华,等.慢传输性便秘结肠Cajal间质细胞减少与细胞凋亡的关系[J].第三军医大学学报,2004,26(12):1049-1051
    32 Dhamija R, Tan K M, Pittock S J, et al. Serologic profiles aiding the diagnosis of autoimmune gastrointestinal dysmotility[J]. Clinical Gastroenterology and Hepatology,2008, 6(9):988-992
    33 胡智,王吉.老年人便秘的危害与防治[J].实用心脑肺血管病杂志,2010,18(7):975-975
    34 Dykes S, Smilgin-Humphreys S, Bass C. Chronic idiopathic constipation:a psychological enquiry[J]. European journal of gastroenterology & hepatology,2001,13(1):39-44
    35 Cummings J H. The effect of dietary fiber on fecal weight and composition[J]. CRC handbook of dietary fiber in human nutrition,2001,3:183-252
    36 Bannister J J, Davison P, Timms J M, et al. Effect of stool size and consistency on defecation[J]. Gut,1987,28(10):1246-1250
    37 周仲瑛.中医内科学.北京:中国中医药出版社.2003.261
    38 方药中,邓铁涛,李克光,等.实用中医内科学.上海:上海科学技术出版社.1986.244
    39 雷威.便秘证候及证候要素分布规律的现代文献研究[J].中医文献杂志,2012(3):53-53
    40 李可,刘敏.功能性便秘中医证候分布研究[J].中国中医药信息杂志,2009,16(12):24-26
    41 王发渭,于有山.高辉远老中医运用白芍配伍12法简介[J].福建中医药,1994,25(5):7-9
    42 黄昌惠.芍药甘草汤治疗老年性便秘96例[J].中国民间疗法.2003,11(5):46
    43 李宪科,王元珍.芍药甘草汤治疗老年人便秘30例[J].医学理论与实践.1998,11(9):402
    44 姜秀举.芍药甘草汤治疗抗精神病药所致便秘的对照研究[J].中国社区医师.2009,11(19):120
    45 赖崇杰.芍药甘草汤及其加减治疗习惯性便秘50例[J].新中医.2001,33(5):61
    46 徐晓蓉,代建华,赵钢.芍药甘草汤加减治疗气血虚弱型习惯性便秘60例[J].四川中 医.1997,15(6):30-31
    47 肖垄.白芍总苷在自身免疫性疾病中的应用[J].中华临床免疫和变态反应杂志,2008,2(1):55-60
    48 曹兰芳,赵瑜,毛海英,等.白芍总苷胶囊治疗儿童特发性关节炎的临床有效性和安全性观察[J].中华风湿病学杂志,2006,10(2):100-103
    49 齐微,孙茜,封雷.芍药甘草汤治疗习惯性便秘的实验研究[J].实用药物与临床,2006,9(3):139-141
    50 韩坚,钟志勇,景丽,等.芍药甘草汤对肠道运动的作用观察[J].广州中医药大学学报,2007;24(1):55-58
    51 Yu H Y, Liu M G, Liu D N, et al. Antinociceptive effects of systemic paeoniflorin on bee venom-induced various 'phenotypes' of nociception and hypersensitivity[J]. Pharmacology Biochemistry and Behavior,2007,88(2):131-140
    52 Zhang X, Li Z, Leung W, et al. The Analgesic Effect of Paeoniflorin on Neonatal Maternal Separation-Induced Visceral Hyperalgesia in Rats[J]. The Journal of Pain,2008,9(6): 497-505
    53 王亚旭,时德.慢性输性便秘结肠阿片受体的病理生理改变[J].中华胃肠外科杂志,2002,5(1):70-72
    54 于文胜,马涛,刘健,等.2.126芍药甙对胃肠平滑肌细胞动力的影响及其信号转导途径的研究[J].基础医学与临床,2003(z1):111
    55 Mao Q Q, Ip S P, Tsai S H, et al. Antidepressant-like effect of peony glycosides in mice[J]. Journal of ethnopharmacology,2008,119(2):272-275
    56 Qiu F M, Zhong X M, Mao Q Q, et al. Antidepressant-like effects of paeoniflorin on the behavioural, biochemical, and neurochemical patterns of rats exposed to chronic unpredictable stress[J]. Neuroscience letters,2013,541:209-213
    57 童卫东,张胜本,张连阳,等.慢传输型便秘结肠肌间丛NOS, SOM,5-HT免疫反应性变化[J].中华胃肠外科杂志,1999,2(3):168-170
    58 王丽雯,袁昉,魏伟.重组人白细胞介素对人外周血淋巴细胞功能的影响及芍药苷的作用[J].中国临床药理学杂志,2009(2):129-133
    59 王朝晖,赵延红,肖美芳,等.大鼠便秘模型制作的初步实验研究[J].现代中医药, 2004(3):53-54
    60曾群,赵果毅.舒通胶囊对燥结型便秘通便功能的研究[J].中国实验方剂学杂志,2010,16(18):139-141
    61 朱军,赵克,李致富,等.冰水灌胃应激建立便秘表现肠功能紊乱大鼠模型[J].胃肠病学,2011,15(12):738-740
    62 Kakino M, Tazawa S, Maruyama H, et al. Laxative effects of agarwood on low-fiber diet-induced constipation in rats[J]. BMC complementary and alternative medicine,2010, 10(1):68
    63 彭成,王岚,赵小梅.SD大鼠阳虚便秘模型的建立及评价[J].中国药理学通报,2007,23(3):407-409
    64 邹颖,郑学宝,戴世学,等.小鼠脾虚便秘模型的建立[J].北京中医药,2009,28(1):60-62
    65 陈芳,石米扬.硫糖铝致便秘作用机制的研究[J].中国药师,2004,7(8):601-602
    66 许海尘,林琳,张红杰,等.慢传输型便秘模型的建立及其机制探讨[J].医学研究生学报,2004,17(6):502-505
    67 刘海峰,何俊堂,汪兴伟,等.大鼠慢传输型便秘模型的建立及其结肠肌电变化检测[J].武警医学,2005,15(12):887-891
    68 郑倩.便秘动物模型的研究进展[J].临床消化病杂志,2012,24(3):189-191
    69 Bharucha AE, Phillips SF. Slow transit constipation.Gastroenterol Clin North Am. 2001,30(1):77-95
    70 李勇,王健,李毅平,等.芪榔合剂对慢性传输型便秘小鼠结肠SP、VIP的影响[J].世界华人消化杂志,2008,16(3):272-276
    71 袁盛榕.药理学实习教程[M].北京:世界图书出版公司,1994:13
    72 张莉华,方步武.脑肠轴及其在胃肠疾病发病机制中的作用[J].中国中西医结合外科杂志,2007,13(2):199-201
    73黄波,陈畅.一氧化氮的功能及其作用机制(I)——性质与功能[J].生物物理学报,2012,28(3):173-184
    74 肖开春,童荣生Cajal间质细胞与胃肠动力关系的研究进展[J].中国药房,2013,24(5):470-472
    75 Faussone-Pellegrini M S. Relationships between neurokinin receptor-expressing interstitial cells of Cajal and tachykininergic nerves in the gut[J]. Journal of cellular and molecular medicine,2006,10(1):20-32
    76 Koh S D, Kim T W, Jun J Y, et al. Regulation of pacemaker currents in interstitial cells of Cajal from murine small intestine by cyclic nucleotides[J]. The Journal of physiology,2000, 527(1):149-162
    77 Shafik A, Ahmed I, El Sibai O, et al. Interstitial cells of cajal in reflux esophagitis:role in the pathogenesis of the disease[J]. Medical science monitor:international medical journal of experimental and clinical research,2005,11(12):BR452-6
    78 Epperson A, Hatton W J, Callaghan B, et al. Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal[J]. American Journal of Physiology-Cell Physiology, 2000,279(2):C529-C539
    79 Torihashi S, Ward S M, Sanders K M Development of c-Kit-positive cells and the onset of electrical rhythmicity in murine small intestine[J]. Gastroenterology,1997,112(1):144-155
    80 Vanderwinden J M, Rumessen J J, Bernex F, et al. Distribution and ultrastructure of interstitial cells of Cajal in the mouse colon, using antibodies to Kit and Kit W-lacZ mice[J]. Cell and tissue research,2000,302(2):155-170
    81 张翠,王博,蔡璇,等.阴离子交换蛋白2功能异常对结肠分泌及蠕动功能的影响[J].上海交通大学学报(医学版),2010,30(7):788-792
    1 DouglasA.Drossman.罗马Ⅲ功能性胃肠病.北京:科学出版社.2008,456
    2袁震土,孙卫东.辨证治疗中青年妇女慢性功能性便秘体会[J].浙江中医杂志,2013 (8):558-558
    3赵景明.辨证治疗结肠慢传输型便秘78例.中国中医药现代远程教育,2013,11(4):39
    4吕长青.辨证治疗功能性便秘50例观察[J].实用中医药杂志,2012,28(8):646-647
    5朱超.功能性出口梗阻性便秘的中医辨证论治[J].四川中医,2012,30(7):37-38
    6叶俏波,陈西平.陈潮祖从气津论治慢性便秘经验[J].四川中医,2009 (11):9-10
    7李国栋,冯丽鹏.辨证论治慢性功能性便秘经验谈[J].北京中医药,2012,31(8):580-581
    8王荣,胡晓阳.段富津教授运用复方芸归汤治疗便秘的经验[J].中医药信息,2011,28(1):30-31
    9黎晓武,姜雨含,程亚南.醒脾饮治疗小儿功能性便秘54例[J].中国中医药现代远程教育,2013,11(21):17-18
    10于坤.润肠汤治疗老年性便秘的临床探讨[J].光明中医,2013,28(10):2095-2096
    11卢乐声,钟华,胡凌伟,等.润肠行气醒脾汤治疗婴儿便秘38例临床观察[J].浙江中医杂志,2013(10):742
    12薛维华,张燕,丁敏.七星针加体针治疗特发性便秘78例[J].中国针灸,2006,25(7):468-468
    13李琰琴.头针配合腹针治疗中风后便秘50例[J].上海针灸杂志,2010,29(6):394-394
    14张银开.腹结穴埋针治疗糖尿病便秘临床观察[J].上海中医药杂志,2011,45(1):66-67
    15陈素华.火针结合加味济川煎治疗老年性阳虚便秘研究[J].海峡药学,2012,24(12):195-196
    16沙淑艳,顾爱焕.腹针配合艾灸治疗老年髋部骨折患者术后便秘的效果观察[J].护理实践与研究,2013,10(3):38-39
    17周波,王伊莞,俞伟君,等.骶四针治疗习惯性便秘的疗效观察[J].中国中医药科技,2013(2):193-194
    18孙冬梅,郭丽,赖新生.芒针深刺中脘穴治疗慢性功能性便秘临床研究[J].浙江中医药大学学报,2012,36(7):812-814
    19张晓华,邓秋生.小针刀治疗慢性便秘25例[J].中国针灸,2009(1):39-39
    20董升,梁振新.三部推拿治疗脾虚气弱型便秘32例[J].中医临床研究,2011,3(001):22-22
    21李小红,李越,陈福洪,等.郑氏经穴腹部按摩对预防骨折卧床患者功能性便秘的效果[J].齐鲁护理杂志:下旬刊,2012 (8):10-11
    22周梅娟.穴位按摩对改善剖宫产术后腹胀便秘的临床研究[J].护理实践与研究,2009,6(3):25-26
    23杨丽春,高玉霞,田迎春,等.冠心病患者足底按摩与药物治疗便秘效果的观察[J].现代护理,2006,12(12):1111-1112
    24宋磊雁.穴位按摩治疗虚证便秘疗效观察[J].护理学杂志:综合版,2009,23(12):41-42
    25冯秀珠,黄春燕,苏海丹.脐周按摩治疗老年人便秘效果观察和护理干预[J].护士进修杂志,2005,20(4):347-348
    26刘华,万桃红,周小兰.掐压商阳穴和腹部按摩对骨科患者便秘的护理[J].实用临床医学(江西),2013(1):113-114
    27郑少康,彭林,林锡,等.补中益气汤保留灌肠联合西药治疗气虚型出口梗阻型便秘.实用中医内科杂志,2013,27(7):133-135
    28孙健,林晖.中药保留灌肠结合西沙比利对虚证型慢传输型便秘患者肛门动力学的影响.上海中医药杂志,2012,46(12):30-32
    29韩艳,马红梅,朱亚萍.中药肠毒清保留灌肠治疗老年顽固性便秘的体会[J].湖南中医药导报,2004,9(11):29-30
    30李萍,朱银萍,杨楼,等.高位灌肠法治疗结肠慢传输性便秘的疗效观察[J].南方护理学报,2001,8(6):41-42
    31胡团敏,张丽婷,黄永德.黄术灌肠液结合大肠水疗治疗老年性便秘疗效探讨[J].医学理论与实践,2010,23(1):15-16
    32潘洁玲,王澍欣,林凯玲,等.穴位敷贴治疗实证便秘30例疗效观察[J].新中医,2008,40(3):68-69
    33魏素兰,徐向红.大黄米醋敷贴治疗老年糖尿病便秘132例[J].浙江中医杂志,2008,43(3):158-158
    34余波,刁本恕.中药通便膏敷贴穴位治疗便秘经验[J].中医外治杂志,2006,14(5):46
    35陈睿.神阙穴敷贴治疗便秘[J].中国针灸,2002,22(8):540-541
    36吴坚芳,许邹华,徐进康.穴位敷贴治疗功能性便秘50例临床观察.江苏中医药,2013,45(9):61
    37陈硕,陈英,林秋芳.经超微粉碎中药神阙穴位敷贴治疗慢性功能性便秘的临床研究[J].光明中医,2013,27(9):1841-1843
    38温建军,卢冬燕,陈爱芳.中药敷贴疗法对老年人便秘的临床疗效观察[J].中国民族民间医药杂志,2011,19(24):114-115
    39季海刚.中药脐部敷贴治疗心血管病监护患者便秘的疗效观察[J].光明中医,2009,24(2):289-290
    40刘春红,李艳,刘淑珍,等.应用中药敷贴治疗150例骨科卧床便秘患者的疗效观察[J].求医问药:下半月刊,2012,9(11):601-602
    41于永铎,陈萌,辛世勇,等.强化穴位埋线治疗慢传输型便秘的临床疗效观察.中国医学工 程,2013,21(12):29-30
    42彭辉,刘建平.穴位埋线治疗结肠慢传输型便秘32例[J].现代中医药,2013,33(1):54-55
    43曲牟文,李国栋,洪子夫,等.八髎穴埋线治疗慢传输型便秘30例临床观察.中医杂志,2013,54(19):1663-1665
    44张舒雁,龚秀杭,季聪华,等.简易穴位埋线法治疗习惯性便秘疗效观察[J].中华中医药学刊,2012,30(6):1286-1288
    45刘志霞,龚旺梅,刘志宏.穴位埋线治疗慢传输型便秘25例[J].中医研究,2012,25(6):60-62
    46丁杰,刘树军.穴位埋线治疗慢传输型便秘50例临床观察[J].辽宁中医药大学学报,2011,13(5):218-219
    47邹春萍,陈兴华.长强穴埋线为主治疗盆底肌失驰缓所致便秘108例临床观察[J].实用中西医结合临床,2012,12(001):65-66
    48冯雯,范一宏,吕宾.慢传输型便秘发病机制的研究[J].胃肠病学,2012,17(5):311-313
    49郑学宝,叶秋丽,戴世学,等.枳术汤对脾虚便秘小鼠5-羟色胺受体4和生长抑素基因的靶向调控[J].中药药理与临床,2009,24(6):3-5
    50岳春花.四磨汤对慢传输型便秘大鼠结肠五羟色胺兴奋性受体的干预研究[D].浙江中医药大学,2010
    51周永学,王欢.通便玉蓉丸对便秘小鼠胃肠功能及5-羟色胺含量的影响[J].时珍国医国药,2013(1):116-117
    52高健群,巫全胜,钱宁,等.肃肺润肠汤对药物依赖性便秘大鼠大肠杯状细胞,5-HT变化的实验研究[J].时珍国医国药,2010,21(7):1814-1815
    53郑晨果,叶乐驰,金纯.丹参枳术饮对STC大鼠肠道肌间神经丛内VIP, SP表达的影响[J].中国中医急症,2010(010):1737-1738
    54范一宏,徐国萍,冯雯,等.枳术通便汤对慢传输型便秘大鼠结肠墨汁推进率,GDNF及NOS mRNA表达的影响[J].中国中西医结合杂志,2012,32(4):486-489
    55孟萍,尹建康,高晓静,等.白术对慢传输型便秘大鼠结肠组织Cajal间质细胞的影响[J].中医研究,2012,25(9):58-60
    56孙建华,郭慧,陈璐,等.电针“天枢”穴对慢传输型便秘大鼠结肠平滑肌结构及Cajal间质细胞的影响[J].针刺研究,2011,36(3):171-175