四逆散促胃肠动力作用及其作用机制的实验研究
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
     功能性消化不良(Functional Dyspepsis, FD),是由非器质性病变引起的一组消化不良症候群。FD的发病机制至今尚未完全明了,现代医学主要采用促胃肠动力药予以治疗,虽有一定的疗效,但同时也有不同程度的副作用。FD属于祖国医学“胃痛”、“痞证”、“纳呆”、“嘈杂”、“胃缓”、“呕吐”、“呃逆”等证的范畴,近些年来,应用中医药治疗FD取得了显著的疗效。FD以肝郁气滞,脾运失职,胃失通降为其基本病机,因此,本课题采用疏肝理气的代表方四逆散,从胃排空、小肠推进、神经元、神经递质的角度,来探讨其促胃肠动力的作用及作用机制。
     本课题通过对正常小鼠胃内葡聚糖蓝-2000残留量、小肠内葡聚糖蓝-2000推进率,来研究四逆散对小鼠胃排空、小肠推进的影响;通过采用正常大鼠肠道气囊法,记录正常大鼠用药后肠收缩幅度和频率的变化;采用医学彩色图象全自动分析系统,分析用药后正常大鼠胃窦组织中NOS(Nitric xidesynthase)阳性神经元分布面积和酶活性的变化;采用硝酸酶还原法和比色法,检测用药后正常大鼠胃窦组织中NO(Nitric Oxide)和TchE(True choline esterase)的含量变化,通过以上几个方面,研究四逆散的促胃肠动力作用及其作用机制。
     方法
     取30只健康的昆明种小白鼠,体重20±2g,雌雄各半;30只健康的SD系大白鼠,体重200±20g,雌雄各半。随机分为四逆散组、莫沙比利组和生理盐水组三组,每组10只。分别观察四逆散,莫沙比利和生理盐水对小鼠胃排空、小肠推进的影响,对大鼠肠收缩幅度和频率的影响,对大鼠胃窦组织中NOS阳性神经元分布面积和酶活性的影响,以及对大鼠胃组织中NO、TchE含量的影响。各组数据均采用均数±标准差((?)±s)表示,用SPSS统计软件进行数据处理,单因素方差分析,均采用组间两两比较。
     结果
     1.对小鼠胃内色素残留量的影响中,四逆散组与莫沙比利组比较无显著性差异(p>0.05),与生理盐水组比较有非常显著性差异(P<0.01);莫沙比利组与生理盐水组比较有非常显著性差异(P<0.01)。
     2.对小鼠小肠色素推进率的影响中,四逆散组与莫沙比利组比较无显著性差异(P>0.05),而与生理盐水组比较有显著性差异(P<0.05);莫沙比利组与生理盐水组比较有非常显著性差异(P<0.01)。
     3.对大鼠肠收缩幅度和频率的影响中,四逆散组与生理盐水组比较有非常显著性差异(P<0.01),与莫沙比利组比较无显著性差异
    
    四逆散促胃肠动力一作用及其作用机制的实验研究
    硕士论文
    (P>0.仍);莫沙比利组与生理盐水组比较也有非常显著性差异
    (P<0 .01)。
     4.对大鼠胃窦组织中NOS阳性神经元分布面积和酶活性的影响中,
    四逆散组与莫沙比利组比较无显著性差异(P>0.05),而与生理盐水组
    比较有非常显著性差异(P<0.01);莫沙比利组与生理盐水组比较也有
    非常显著性差异(P<0.01)。
     5.对大鼠胃窦组织NO,TchE含量的影响中,四逆散组与莫沙比
    利几组比较有非常显著性差异(P<。.01),与生理盐水组比较无显著性差
    异(P>0.05);莫沙比利组与生理盐水组比较有非常显著性差异(P<仪
    01)。
    结论
     四逆散可促进胃排空、小肠推进,从而促进胃肠动力。
     四逆散的促胃肠动力作用机制可能是:
     (1)加快肠收缩频率并升高其收缩幅度,从而推进肠蠕动,防止肠
    动力障碍,协调胃十二指肠运动。
     (2)使胃窦壁NOS阳性神经元分布面积减少,活性降低,从而减少
    非肾上腺素非胆碱能神经元(non一adrennergie non一eholinergie NANc)抑
    制性神经递质NO的生成,从而增强胃肠道平滑肌的兴奋性,促进胃排
    空。
     (3)增加胃组织中兴奋性神经递质Aoh的水解酶T比E含量的同时
    降低胃组织中抑制性神经递质NO的含量,促进胃收缩.
Object:
    Dysfunctional Dyspepsia is a group of dyspepsia symptoms caused by nonorgan pathological changs.The cause of it does not definite.So far,we have beening lakeing effective remedies for curing it. There is no name about the illness in the TCM,but according its clinical symptom, it belong to the syndrome of the stomachache, the stuffiness in the stomach,the scarcity desire of the dining, the gastric upset, the frequent vomiting, the spewing, the hiccup and so on.The fundamental pathogenesis of it is the liver-qi stagnation the spleen-qi deficiency and the stomache-qi ascending adversely. During this years, TCM has a prominent effect on Dysfunctional Dyspepsia,so we study the effect of SiNiSan of soup on the Dysfunctional Dyspepsia sharply from the ability of stomach emptying and the ability of intestines pussing on the normal Kunming rats by the coloring matter,and the chang of the nerve fiber, nerve qualitative, on the stomach organize of normal SD rats
    Methods:
    In the experiment, the thirty Kunming rats, whose avoirdupois are about twenty grammes,and thirty S. D rats, whose avoirdupois are about two hundred grammes,were randomly divided into three groups, 0. 9yS group, SiNiSan of soup group and Mosapride Citrate group. Every gro-up had ten rats and was dealed with water, SiNiSan of soup and Mosa-pride Citrate. At last,we study the effect of the ability of stomach emptying and the ability of intestines pussing on the Kunming rats.An-d we study the chang of the intestines constract scope and frequency of the norml SD rats, the chang of the nerve fiber, the nerve qualitative, on the stomach organize of the normal SD rats The statistical method are F test and Q test.
    Result:
    The experiment of gastric emptying rate on mouse has showed thatSiNiSan of soup could promote he gastric mptying ate,there was very remarkable differentce between the SiNiSan of soup group and the normal group (p<0.01),and there was not significant difference between the SiNiSan of soup group and the Mosapride Citrate group (p>0. 05). And there was very remarkable difference
    
    
    between the Mosap-ride Citrate group and the normal group(p<0. 01).
    The experiment of intestines pussing rate on rat has showed that SiNiSan ofsoup could promote the intestines pussing rate, there was remarkable difference between the SiNiSan of soup group and the norma 1 group(p<0. 05),and there was not significant difference between the SiNiSan of soup group and the Mosapride Citrate group(p>0.05).And there was very remarkable difference between the Mosapride Citrate group and the normal group(p<0. 01).
    The experiment of the intestines constract scope and frequenc has showed that SiNiSan ofsoup could promote the intestines constract scope and frequenc, there was very remarkable difference between the SiNiSan of soup group and the normal group(p<0. 01),and there was not significant difference between the SiNiSan of soup group and the Mosapride Citrate group(p>0. 05).And there was very remarkable difference between the Mosapride Citrate group and the normal group (p<0. 01).
    The experiment of the NOS masculine nerve fiber distributing area and enzyme active that SiNiSan ofsoup could reduce the NOS masculine nerve fiber distributing area and enzyme active there was very remarkable difference between the SiNiSan of soup group and the normal group (p<0. 01), and there was not significant difference between the SiNiSan of soup group and the Mosapride Citrate group(p>0,05).And there was very remarkable difference between the Mosapride Citrate group and the normal group(p<0. 01).
    The experiment of the stomach organize NO, TchE content has showedthat SiNiSan ofsoup could reduce NO content and promote tHe TchE content there was very remarkable difference between the SiNiSan of soup group and the normal group (p<0. 01), and there was not significant difference between the SiNiSan of soup group and the Mosapride Citrate group(p>0. 05). And there was very remarkable difference between the Mosapride Citrate group and the normal group (p<0. 01).
    Conclusion:
引文
[1] 林江,等.功能性消化不良的发病机理研究进展.胃肠病学,1997;2(1):50-53
    [2] Ke MY, GU CM.Functionnnnal dyspepsia:Pathogenesis and managemen.proceedings of 1996 Shanghai International Conference of Gastroenterology, Shanhai,China. 1996;28-30
    [3] 余跃,侯晓华,等.非溃疡性消化不良患者胃窦壁内NO能、VIP能神经与胃排空关系的研究.中华消化杂志,1988;18(5):291-294
    [4] TestoniPA..Interdigestiveantroduodenalmo-tordisordersinfuntion aldyspepsia. Associat-edchronicgastritiscorrelateswithafurthermotorimpairmentl..Gastroenterol, 1992;24:440
    [5] 吴颖敏.功能性消化不良与幽门螺杆菌关系探讨.广东药学院学报,1998,(2):103-105
    [6] 王承党,莫剑忠,萧树东.功能性消化不良发病机理的研究进展.国外医学(消化系疾病分册),1996;16(4):217-219
    [7] ParkmanHP, Miller MA,Trate D,et al Ultrasonography and gasttic emptying scientigraphy are complementary for assessment of dys pepsia .J Clin Gastroenterol 1997;24(4):214-219
    [8] Marzio L.Ralationship Between gastric and gallballer emptying and refilling in normal subject and patient with H.Pylori positive and negative. Gut, 1995;36(7):23-30
    [9] Rhee PL,Kim YH,Son HJ,etal Lake of assosiation of Helicobater pylori infection with gastric hypersensitivity or delayed gastric emptying in functional dyspepsia. Am J Gastroenterol ,1999;94(11):3165-3169.
    [10] Code, C.F. et al.: The interdigestive myoelectric eomplex of the stomach an small bowell of dogs. J. Physiol, 1975;246: 289.
    [11] Locke, G.R. and Talley, N.J.:Management of non-ulcer dy spepsia: J. Gastroenterol. Hepatol. 1993; 8: 279-286.
    [12] Jibbnk, H, J. A., Smont, A. L. P. M., van. Berge-Hengonwen, G. P.;Pathophysiology. and. treatment, of. functional dyspepia. Scand, J.Gastroenterol. 1993; 28 (suppl 2000): 8-14.
    [13] 柯美云,战淑慧.功能性消化不良的发病机理.中国实用内科杂志。1995,15:7-8。
    [14] Talley, N. J. Phillips, F.: Non-ulcer: dyspeps ia: Potential causes and pathophysiology. Ann. interm. Med. 1988; 108:865-879
    [15] 杨春敏,周吕.健康人和功能性消化不良病人胃移行性复合运动与胃电图的关系及胃动素变化.中华消化杂志。1997;17:42—43。
    [16]] Chakder, S. and Rattan, S.:Release of nitric oxide by activation of nonadrenrgic noncholinergic neurons of internal
    
    anal sphincter. AM.J. Physiol. 1993;264:G7-G12.
    [17] Navin, A.and Paterson, W.G.,:Role of nitric oxide in esophageal peristalsis. Am.J. Physiol. 1994;266:G123-G131.2P15
    [18] Rodriguez-Membrilia, A.,Martinez, V.,Jimenez, M.,Gonalon s,E.,Vergara. P.;is nitric oxide the finalmediator regulating myoelectric complex cycle?Am.J. Physiol. 1995;268:G207-G214
    [19] 陈文柳,戴益琛.功能性消化不良胃动力学类型与胃液一氧化氮水平.临床消化杂志.2002;14(2):17
    [20] 于家军,李寿山.治疗功能性消化不良经验.辽宁中医杂志.1998;25(6):2554
    [21] 姚明全.和胃通气汤治疗功能性消化不良腹胀.湖北中医杂志.1999;21(6):2685
    [22] 吴敏.理气活血汤治疗功能性消化不良.湖北中医杂志.2000;22(5):286
    [23] 蒙旭光.功能性消化不良的中医治疗现状及展望.河北中医.1997;19(5):433
    [24] 谢建群,龚雨萍,陆雄.功能性消化不良的中医辨证论治.上海中医药杂志,1998;32(5):166
    [25] 金群,王爱民,张旭初.功能性消化不良分型辨治初探.南京中医药大学学报,1998;14(3):1767
    [26] 麦燕芳.中医辨证分型治疗功能性消化不良56例疗效观测.国医论坛,1999;14(3):304
    [27] 黄可成,陈寿菲,肖丽春,等.非溃疡性消化不良的分型论治.实用中西医结合杂志,1997;10(19):18695
    [28] 陈自愚,赵青.枳实消痞汤治疗功能性消化不良125例疗效观察.湖南中医杂志,1999;15(2):98
    [29] 梁开发.枳实消痞丸加减治疗非溃疡性消化不良76例.四川中医,1998;16(7):269
    [30] 沈明.温胆汤治疗功能性消化不良42例.河南中医,2000;20(4):5010
    [31] 沈世应,莫测.丹栀逍遥散治疗功能性消化不良39例临床观测.安徽中医临床杂志,2000;12(1):3811
    [32] 姜周明.芍药甘草汤治疗溃疡样型功能性消化不良30例.浙江中医杂志,2000;35(3):10012
    [33] 刘同亭,赵立群,薛吉栋,等.四磨汤加味治疗非溃疡性消化不良临床研究.山东中医药大学学报,1999;23(1):3913
    [34] 谈娴娴,钱玉凡.越鞠丸加减治疗功能性消化不良120例临床观测.新中医,1998;30(1):1814
    [35] 应瑛.加味—贯煎治疗功能性消化不良120例.浙江中医杂志,1998;33(3):10915
    [36] 卓家和,郑立升.六君子汤治疗功能性消化不良60例.中国中西医结合脾胃杂志,1999;7(1):2916
    
    
    [37] 王国建.半夏泻心汤治疗非溃疡性消化不良50例.中医研究,1999;12(2):4317
    [38] 潘金辉,黄坚,黄文锋.疏肝和胃汤治疗功能性消化不良122例临床观察.湖北中医杂志,2000;22(2):1318
    [39] 吴敏.理气活血汤治疗功能性消化不良.湖北中医杂志,2000;22(5):2819
    [40] 吴乃光.理气开郁方治疗功能性消化不良疗效观察.上海中医药杂志,2000;34(5):1720
    [41] 朱生梁,方盛泉,黄蔚.疏肝健胃方治疗功能性消化不良的临床研究.上海中医药杂志,2000;(4):3021
    [42] 刘红书,徐文贞.和胃健运汤治疗功能性消化不良60例.国医论坛,1999;14(3):3722
    [43] 汪艳娟,王行宽.连苏畅中饮治疗功能性消化不良的临床观察.湖南中医学院学报,1999;19(1):3723
    [44] 李子俊,黄松柏,吴丽桑,等,金龙汤治疗非溃疡性消化不良的临床研究.中国中西医结合脾胃杂志,1999;7(1):1924
    [45] 孙维峰,徐伟,康国治,等.升降汤治疗功能性消化不良的临床与实验研究.中国中西医结合脾胃杂志,1998;6(3):145
    [46] 尚云.和胃健运汤治疗非溃疡性消化不良的临床观察.中医杂志,1998;39(3):16826
    [47] 尹惠群,欧阳瑶,徐平,等.六味安消治疗功能性消化不良疗效观察.中国中西医结合脾胃杂志,1999;7(5):31427
    [48] 钟惠闽,许自明,郑刚,等.复方褐藻胶囊治疗功能性消化不良的临床观察.中国中西医结合脾胃杂志,1998;6(3):18128
    [49] 黄亚芳.气滞通胶囊治疗功能性消化不良182例.河北中医,2000;22(6):43429
    [50] 林锦生,等.中西医结合治疗非溃疡性消化不良疗效观察.中国中西医结合脾胃杂志,1996;4(1):58.
    [51] 朱耀群,等.中西医结合治疗功能性消化不良106例.实用中西医结合杂志,1997;10(1):12—13.
    [52] 王启之,等.四磨汤和西沙必利治疗功能性消化不良的临床观察.中国中西医结合脾胃杂志,2000;8(1):29
    [53] 陈广娥,顾兴江,谭善瑞.针灸治疗功能性消化不良疗效观察.中国针灸.2000;20(6):345
    [54] 艾宪君.中药加针灸及TDP治疗功能性消化不良60例.陕西中医,2000;21(6):248
    [55] 郭明.胃电治疗功能性消化不良的临床观察.陕西中医学院学报,1998;21(1):47
    [56] 陈震,田桂卿,等.参夏和胃宁治疗非溃疡性消化不良的临床与实验研究.中国中西医结合杂志,1994;(2):83
    [57] 陈震,李世荣,等.复方半夏胶囊治疗非溃疡性消化不良的疗效观察.中医杂志,1994;(5):292
    
    
    [58] 陈震,李世荣,薛淑锦,等,健脾消食丸治疗非溃疡性消化不良50临床观察.中国医药学报,1990;(3):46
    [59] 严光俊.辨证治疗功能性消化不良84例临床观察.上海中医药杂志,1997(3):8
    [60] 李秀峰,等,半夏泻心汤对顽固性非溃疡性消化不良的动力影响,中国中西医结合杂志,1994;(11):72
    [61] 陈多,等.旋覆代赭汤促胃肠动力作用研究.中药药理与临床,1997;(1):4
    [62] 邱赛红,等.芳香化湿药开胃作用机理的实验研究.中药药理与临床,1997;(2):1
    [63] 任平,等.四君子汤对脾虚大鼠胃动素及川芎嗪药物动力学特征的影响.中国中西医结合杂志,1997;(1):45
    [64] 任金刚,等.胃病Ⅰ号治疗胃排空障碍的临床观察和实验研究.中国中西医结合脾胃杂志,1994;(1):25
    [65] 马晓松,等.白术对动物胃肠运动的作用及其作用机理的探讨.中华消化杂志,1996;(5):26
    [66] 江汉才,等.越鞠保和冲剂治疗胃排空障碍40例临床观察.中国中西医结合脾胃杂志,1996;(2):76
    [67] 李永渝,等.健胃灵作用机理的研究.中国中西医结合杂志,1992;(1):32
    [68] 李岩,等.芍药甘草汤、四逆散对胃排空及小肠推进功能影响的拆方研究.中华消化杂志,1996;(1):18
    [69] 许鑫枢.消胀冲剂治疗慢性胃炎47临床观察.中国中西医结合脾胃杂志,1993;(1):54
    [70] 李增烈.功能性消化不良的诊断与治疗.临床汇萃,1995;(1):5
    [71] 聂丹丽,等.胃动灵对肝郁,脾虚大鼠模型胃肠运动影响的实验研究陕西中医,2000;21(6):283
    [72] 张沁园,等.肝失疏泄对小肠吸收功能的影响的实验研究 北京中医药大学学报,1999;22(4):31-33
    [73] 周大桥,等.肝郁患者植物神经功能状态探讨 湖北中医杂志,1991;13(1):41
    [74] 余莉芳,等.中医辨证治疗非溃疡性消化不良的探讨 中医杂志,1994;(2):89-91
    [75] 王唏心.理气法在治非溃疡性消化不良中的应用 中医药研究,1991:(16):26
    [76] 李乾构,等.功能性消化不良的辨证论治.北京中医,1996;(1):15
    [77] 陈寿菲,等.疏肝健脾法治疗功能性消化不良71例临床观察福建中医,1997;(1):2
    [78] 徐仁莲.功能性消化不良证治体会.山西中医,1996;(1):51
    [79] 卜平,等.疏肝健脾法治疗肝郁脾虚功能性消化不良疗效观察
    
    中国中西医结合脾胃杂志,1996;(3):134
    [80] 张国梁,理胃舒治疗老年非溃疡性消化不良32例 安徽中医学院学报,1994;(4):13—14
    [81] 况玲.枳实对绵羊小肠电活动的影响 中医药研究,1997;13(3):49
    [82] 张煜,等.治肝药对胃肠道生物电及血流量的影响 中国医药学报,1989;4(2):26—28
    [83] 彭成,等.四逆散治疗功能性消化不良的实验研究.成都中医药大学学报,1999;22(1):39
    [84] 刘风霖.功能性消化不良胃肠动力学研究进展.医学综述,2002;8(9):9-10
    [85] Gu C Ke M,Wang Z.Temporal and spatial ralation of pylorus to antroduldenal motility in functional dyspepsia. Chin Med J,1998;111(10): 906-909