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肾气丸治疗脾肾阳虚型消化性溃疡的实验研究
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摘要
消化性溃疡(peptic ulcer)泛指胃肠道黏膜被胃消化液消化而形成深达黏膜下层的黏膜破损,可发生于食管、胃、十二指肠及胃空肠吻合口、含胃黏膜的憩室内。临床以胃溃疡(gastric ulcer,GU)和十二指肠溃疡(duodenal ulcer,DU)常见,故一般所谓的消化性溃疡是指GU和DU。消化性溃疡在中医属于“胃脘痛"的范畴,对于本病的病因病机,虽然观点不一,但大多数医家认为主要是由于七情刺激、饮食不节、劳倦内伤以及外感六淫,导致脾胃虚弱,肝胃不和,从而升降失常、损伤肠胃,久而成病。《内经》指出:“饮食自倍,肠胃乃伤”,“思伤脾”,“寒气客于肠胃,厥逆上出,故痛而呕也”。《景岳全书》认为“脾胃之伤于情志者,较之饮食寒暑为更多也”。脾胃虚寒,则肝木乘之,肝气犯胃,则脾胃更为虚弱,日久则阳气更虚,变为虚寒之证。而且中气虚弱则气血不通,瘀阻经络,不通则痛。
     从临床观察来看,不论何种类型的消化性溃疡,均以胀痛为主。从消化道病理角度来看,主要机理是胃肠道动力功能障碍。从中医辨证来看,就是脾虚、气滞的一系列症状。其病机病理主要是脾胃升降失常,脾虚、气滞、血瘀。生理上,脾主运化,胃主受纳;脾以升为健,胃以降为和,升降有序,则气机调和,胃气通降是脾胃升降有序的重要环节。在治疗上,不论中、西医治疗消化性溃疡的目标有三方面:(1)止痛;(2)促使溃疡早日愈合;(3)防止复发。在西医则重活动期溃疡的溃疡修复。而针对病人的个体体质,予中医辨证治疗尤为重要。临床中辨证施治有侧重,以脾虚为主者,治疗则健脾益气为主,兼活血化瘀;以气滞为主者,则应行气导滞和胃止痛。而肝与脾胃,相侮相克,相互制约,脾胃一气虚,则易肝木乘脾土。叶天士曰:“木横乘土,中宫受病。”肝郁气滞或胃气壅滞。从气、血辨证方面治疗,就可止痛,促进溃疡愈合和防止复发三方而兼而得之。有利于脾胃功能恢复正常。
     目的:
     在前人使用肾气丸的基础上,透过现代科学理论,科技手段与实验研究来扩大其运用范围。通过实验研究,从组织学观察、病理学观察、胃液分析、溃疡愈合质量(QOUH)四方面研究肾气丸治疗消化性溃疡的作用机制及靶点,揭示肾气丸治疗消化性溃疡损伤及黏膜再生的具体作用机理,为临床应用提供科学依据。多角度评价肾气丸对各种常见消化性溃疡模型的疗效,研究其作用靶点和作用理,为补肾法治疗消化性溃疡提供合理的科学依据,丰富治”胃”病的治法,拓展中医诊断思路。
     方法:造模方法
     1.建立脾肾阳虚动物模型
     2.脾肾阳虚大鼠乙酸烧灼性胃溃疡实验
     3.动物分组及给药:随机分为5组,每组10只:A模型组;B.生理盐水对照组;
     C.雷尼替丁组;D.肾气丸组;E.肾气丸+手参组;。
     4.标本采集和处理
     (1)取一批脾肾阳虚动物造成乙酸烧灼胃溃疡模型后,不行胃内细菌数测定,测其它指标。分组及造模同前。待全部动物实验完毕后一起用放射免疫法测PGE2、EGF、SS与GAS、NO与ET-1表达。
     (2)胃酸及胃蛋白酶的测定:(A)中和法测定胃液总酸度(B)改良Mett法测定胃蛋白酶活性
     (3)胃壁结合黏液含量的测定
     5.观察指标胃液pH值;溃疡面积计算;血清PGE_2、EGF、GAS、NO与ET-1含量;病理观察,并进行光学显微镜下分析。
     6.统计学处理数据统计采用SPSS 13.0进行统计,计量资料多组间比较采用方差分析,组间两两比较方差齐时用LSD检验,方差不齐时用Dunnett's T3检验,计数资料采用X~2检验。
     结果:
     1.观察各组对胃壁结合黏液含量的影响结果显示:运用计算机图像分析测量再生黏膜总面积中PAS阳性面积的百分数。结果胃黏膜表面上皮细胞分泌中性黏液而被染成红色,故呈PAS阳性,雷尼替丁组、肾气丸组、肾气丸+手参组PAS阳性面积明显多于模型组(P<0.05),结果见表3,图1。
     2.各组对血清EGF、GAS的影响结果显示:①模型组与肾气丸+手参组之间EGF值水平差异有显着意义,(P<0.01);②GAS各组均数符合方差齐性,但组间差异并无统计学意义。结果见表4。
     各组对血清PGE2、NO、ET-1的影响结果显示:①模型组与雷尼替丁组、肾气丸组、肾气丸+手参组之间PGE_2值水平差异有显着意义,(P<0.05)。治疗后雷尼替丁组、肾气丸组、肾气丸+手参组明显下降;②模型组与雷尼替丁组、肾气丸组、肾气丸+手参组之间NO值水平差异有显着意义,(P<0.05)。治疗后雷尼替丁组、肾气丸组、肾气丸+手参组明显上升。③各用药组、模型组、生理盐水对照组之间对血清ET-1做比较,模型组与各用药组间的比较都有统计学意义,治疗后雷尼替丁组、肾气丸组、肾气丸+手参组明显下降,其中肾气丸+手参组有非常显着意义(P<0.01)。结果见表5。
     结论:
     有关肾气丸的药理研究报道多从对某一系统或某一病变指标的影响入手,观察该方的治疗效果并探讨作用机制。在实验中,多根据现代医学发病原理进行动物模型的复制或在原有动物模型基础之上稍加改进而制作病理模型,观察内容从症状表现、生命体征、形态学和组织学、各项免疫和生化指标逐渐深入到基因表达。这种研究方法固然可以在一定层面上揭示肾气丸的某些作用靶点和影响机制,但由于中医学特色是辨证论治指导下的整体调节,以“病”为着眼点的中药药理学实验研究方法显然与中医“辨证用药”的治疗准则相差甚远。尽管广大学者在中医证候动物模型的研究领域进行了积极的探索,然而成熟定论的动物模型并不多见。今后若能从改进动物模型入手,发掘现代医学病症和中医辨证分型之间的内在联系,建立中医证候的客观综合指标体系,进而复制出符合该指标体系的中医证候动物模型,从方证对应的角度着手用药,立足整体,将多层次、多靶点的指标检测纳入药物疗效评价标准,采用基因芯片等现代科学技术,从多学科、多系统、多病种的角度探讨药物治疗机制,对于准确把握中药复方的体内作用原理以及客观评价中药复方的治验结果,将会更具说力,有助于推动中医药发展的现代化。
     创新点
     1.首创国内外结合运用中医名方肾气丸加上藏医珍贵药手参来作实验研究。评价与证明了肾气丸及手参治疗脾肾阳虚型消化性溃疡大鼠模型的疗效,发现了其可能的作用机制和靶点,揭示肾气丸治疗消化性溃疡的机理,为进一步的基因和蛋白表达研究奠定基础,为临床应用提供了科学依据。
     2.对于消化性溃疡医家多从脾胃、从肝论治,鲜有从肾论治者。我们以大鼠采用中医证候动物模型造模方法,建立脾肾阳虚型消化性溃疡模型,从组织学观察、病理学观察、胃液分析及细胞因子检测等方面,评价肾气丸治疗脾肾阳虚型消化性溃疡的作用机理,是国内首次进行补肾法治疗消化性溃疡的动物实验研究。
Peptic ulcer(peptic ulcer) refers to the gastrointestinal tract by gastric mucosa and the formation of digestive juice digestive submucosa as deep as the mucosa is damaged,can occur in the esophagus,stomach,duodenum and gastrojejunostomy mouth of the diverticulum with gastric mucosa inside. Clinical to gastric ulcer(gastric ulcer,GU) and duodenal ulcer(duodenal ulcer,DU) common,it generally refers to the so-called peptic ulcer GU and DU.Peptic ulcer in Chinese medicine as "Epigastralgia" areas for the disease pathogenesis,although views vary,but most doctors believe was mainly due to the impassioned stimulation,diet,internal injuries,as well as exogenous tired Six,lead to weak spleen and stomach,hepatogastric not and,thus lifting disorders,gastrointestinal injury,a long time from disease."Neijing" pointed out:"Since the times of eating,gastrointestinal injury is," "think of spleen injury," "cold off at the stomach,the Jue-Inverse out,it is also pain and vomit." "Jing Yue Quan Shu" that "the spleen and stomach injuries in the emotions of those who,for more years than eating it." Cold spleen and stomach,then violations by the liver,Violations by the liver-qi to the stomach,spleen and stomach are more weak and more a long time while yang is true,the evidence becomes cold.And weakness in the blood gas barrier, Blood Meridian,the pain is not General.
     Judging from the clinical observation,regardless of what type of peptic ulcer,are mainly pain,gastrointestinal pathology from the point of view, is the main mechanism of gastrointestinal motility dysfunction.From the TCM perspective,is the deficiency,a series of symptoms of Qi stagnation.Its pathogenesis pathological movements mainly the spleen and stomach disorders, deficiency,Qi stagnation,blood stasis.Physiological,spleen governs transport and satisfied by the main stomach and spleen health to be promoted. Down to the stomach and,landing and taking off in an orderly manner,then reconcile Qi,Wei Qi is the spleen and stomach Tongjiang an important part of movements in an orderly manner.In treatment,whether in the goal of TCM treatment of peptic ulcer is three-fold:(1) pain;(2) to promote ulcer healing as soon as possible;(3) to prevent recurrence.In Western medicine is re-active ulcer ulcer repair.Against the patient's individual physique,to the TCM treatment is particularly important.Differential Treatment of clinical focused to the main deficiency,treatment is mainly Jianpi Yiqi,and promoting blood circulation,mainly to stagnation of qi,the hardship of the liver and spleen.Grams of phase insult each other constraints,the spleen and stomach qi deficiency,liver by soil.Ye Tianshi's said:" Violations of the liver to the spleen and stomach are sick stomach." Wei Qi stagnation of liver Qi stagnation or Pause.From the qi and blood differentiation aspects of treatment,can relieve pain,promote healing and prevent ulcer recurrence and derived from the tripartite and.In favor of the spleen and stomach function returned to normal.
     Objective:
     Shenqi Pill use in the past,based on the use of modern scientific theories, and experimental study of scientific and technological means to expand its scope of application.Through experimental research,from the histological observation,pathological observation,gastric analysis,thequality of ulcer healing(QOUH) Shenqi PillⅣstudy the mechanism of the treatment of peptic ulcer and target,revealed Shenqi Pill mucosal injury and the treatment of peptic ulcer the specific mechanism of regeneration,in order to provide scientific basis for clinical application.Shenqi Pill evaluation of multi-angle on a variety of common peptic ulcer effects model to examine the role of targets and the rationale for the treatment of peptic ulcer Busben law to provide a reasonable scientific basis to enrich the government, "stomach" Disease Treatment and expand ideas of TCM diagnosis Methods:The model approach
     1.The establishment of animal models of kidney-yang deficiency of spleen
     2.Spleen and kidney yang deficiency rats with gastric ulcer
     3.Animal grouping and drug delivery:were randomly divided into 5 groups of 10:A model group;B.saline control group;C.ranitidine group;D.Shenqi pill group;E.Shenqi Pill +RIRr group;.
     4.Specimen collection and processing
     (1) the animals from a group of kidney-yang deficiency of spleen acid burn caused by gastric ulcer,the bacteria can not stomach the determination of other indicators measured.Division and with the former model.All animal experiments to be together after the test by radioimmunoassay PGE2,EGF,SS and GAS,NO and ET-1 expression.
     (2) gastric acid and pepsin determination of:(A) Determination of gastric juice and total acidity(B) Determination of improved Mett pepsin activity
     (3) combined gastric wall mucus determination
     5.Observed gastric pH;ulcer area;serum PGE2,EGF,GAS,NO and ET-1 content;pathological observation,and analysis of optical microscope.
     6.Statistical data using SPSS 13.0 statistical measurement data to compare the use of multiple analysis of variance,22 inter-group homogeneity when compared with LSD test at variance with missing Dunnett's T3 test,the use of count data X2 test.
     The results:
     1.To observe the group of gastric wall mucus content of combined results showed that:the use of computer image analysis measuring the total area of mucosal regeneration in the percentage of PAS-positive area.The results of gastric mucosa surface epithelial cells and mucus secretion by neutral red dye,it was PAS positive,ranitidine group,Shenqi Pill group Shenqi pill + RIRr Group PAS-positive area significantly more than the model group(P<0.05), the results shown in Table 3,Figure 1.
     2.In each group of serum EGF,GAS showed the impact:①the model group with Shenqi pill + RIRr value between the level of EGF significant difference, (P<0.01);②GAS few in each group were in line with the side poor homogeneity, but there is no difference between groups statistically significant.The results in table 4.
     Each group on serum PGE2,NO,Er-1 results showed the impact:①the model group and the ranitidine group,Shenqi Pill group Shenqi pill + RIRr group difference between the PGE2 levels significantly,(P<0.05).Ranitidine group after treatment,Shenqi Pill group Shenqi pill + RIRr group decreased significantly;②model group and the ranitidine group,Shenqi Pill group Shenqi pill + RIRr value between the level of NO There was significant difference,(P<0.05).Ranitidine group after treatment,Shenqi Pill group Shenqi pill + RIRr group was significantly increased.③the medication group, model group,normal saline control group between the serum ET-1 compared with model group,treatment group comparisons are statistically significant, ranitidine group after treatment,Shenqi Pill Group Shenqi pill + RIRr group decreased significantly,which Shenqi pill + RIRr group was significant(P<0.01).The results in table 5.
     Conclusion:
     The Shenqi Pill pharmacological research reports from the system or of a lesion index of a start,observe the side effects of treatment and to explore the mechanism of action.In the experiment,more than modern medicine in accordance with animal models of pathogenesis for a copy of the original animal model or in some improvements based on the production of pathological model, the content from the observation of symptoms,vital signs,morphology and histology,the immune and gradually into the biochemical indicators of gene expression.While this approach can reveal a certain level,some of the role of Shenqi Pill target and impact of the mechanism,but because of characteristics of syndrome differentiation in Chinese medicine,under the guidance of the overall regulation of the "disease" as the focus of experimental study on pharmacology of Chinese medicine obviously with the Chinese "differentiation agents" a far cry from the treatment guidelines. Although the majority of scholars in the TCM Syndrome animal model of an active area of research for the exploration,but the maturity of the animal model findings rare.From the future to improve the animal model can start to explore the disease and modern medicine of TCM Syndrome Types of the intrinsic link between the establishment of the objective of TCM Syndrome comprehensive index system,and then replicate with the index system of TCM Syndrome animal model, from the side perspective permits the corresponding drug,based on a whole will be multi-layered,multi-target detection of indicators included in the evaluation criteria of drug efficacy,the use of gene chips and other modern science and technology,from multi-disciplinary,multi-system perspective of the health of drug treatment mechanism for an accurate grasp of the role of Chinese herbal compound in vivo,as well as objective evaluation of the principle of Chinese medicine composed of government inspection results,will be more said,and help to promote the development of Chinese medicine modernization.
     Innovation
     1.'s First at home and abroad of a combination of Chinese medicine pill side Shenqi precious Tibetan medicine in RIRr to experimental research. Evaluation and proof of participation Shenqi Pill and hand treatment of peptic ulcer spleen rat model of yang-deficiency type of effect and found that the possible role of its mechanism and target in the treatment of peptic Shenqi Pill reveal the mechanism for further gene and protein expression studies to lay the foundation for the clinical application provides a scientific basis.
     2.For peptic ulcer treatment at home from the spleen and stomach,from the Liver,fresh from the kidney of the ruler.We used rat animal model of TCM Syndrome model for ways to build on the spleen yang-deficiency type of peptic ulcer model,from the histological observation,pathological observation,gastric analysis and cytokine detection,the evaluation of treatment of spleen and kidney Shenqi Pill Yang-type mechanism of peptic ulcer, is the first method for the treatment of peptic ulcer Bushen experimental study of animals.
引文
[1]沈鸣.消化性溃疡发病机制、诊断、治疗进展[J].实用儿临床杂志,2006,21,(9):1357-1359
    [2]陈灏珠.实用内科学(第12版)[M].人民卫生出版社,1866-1869
    [3]刘炯.幽门螺杆菌与消化性溃疡关系的研究进展[J].现代消化及介入诊疗,2006,11(2):87-88
    [4]戴幸平,李家邦.消化性溃疡复发的中西医研究进展[J].中国中西医结合消化杂志,2004,12(5):309
    [5]杜锦辉,武文慧.中医药治疗消化性溃疡临床研究[J].中华中西医杂志,2003,4(23)
    [6]宋兴.脱里透毒法治疗慢性消化溃疡初探[J].成都中医药大学学报,1999,22(1):3
    [7]贺俭.益气解毒汤治疗消化性溃疡近期与远期疗效观察[J].山东中医杂志,1999,18(3):114
    [8]程晓峰.中医治疗溃疡病78例[J]..新中医,1997,29(8):45
    [9]陈盘华.情志与消化性溃疡关系探讨[J].中医药研究,2000,16(3):20
    [10]刘小雨.从肺论治顽固性消化性溃疡92例[J]..云南中医药导报,1999,5(3):17
    [11]刘晨波.中医中药治疗消化性溃疡的综述[J].云南中医中药杂志,1999,20(6):43
    [12]郭志玲.中医治疗消化性溃疡45例[J].中国中医药科技,1999,6(5):346
    [13]时得廷.生肌敛疡法治疗消化性溃疡[J].河南中医,2000,20(3):29
    [14]邱世犹,陈文力.消化性溃疡药物治疗进展[J].中华现代医学与临床,2006,4(9):52-53
    [15]王传功,林丽文,齐汝霞.消化性溃疡的治疗进展[J].济宁医学院学报,2006,29(3):90
    [16]臧恒昌,李宏建,张岫美.中国处方药用药手册[M].北京:化学工业出版社,2001.365-367
    [17]王环增.卫生专业技术资格考试指南(药学专业)[M].北京:知识出版社,2001.667-670
    [18]恽海峰,葛惠男.消化性溃疡的中西医结合治疗进展.[J].江苏中医药,2007,39(5):66
    [19]刘悦.消化性溃疡的中医治疗[J].中国实用乡村医生杂志,2004,11(3):4
    [20]雷有昌.消化性溃疡的中医辨证治疗[J].河南中医学院学报,2003,18(1):42-43
    [21]李克强,张国伟,张曼丽.中医辨证治疗老年消化性溃疡60例[J].中医论坛,1998,13(5):37-38
    [22]蔡筱璐.补中益气胶囊抗消化性溃疡复发临床观察[J].广西中医药,2001,24(5):19
    [23]朱筱莲.四逆散加味治疗消化性溃疡98例[J].广西中医药,2001,24(5):40
    [24]马冠军,金鹏.建中活络汤治疗消化性溃疡76例临床分析[J].河南中医,2002,22(4):25-26
    [25]黄英伟.抗溃疡汤治疗消化性溃疡59例[J].中医杂志,2001,42(11):688
    [26]罗清娇.附桂理中汤加味治顽固性十二指肠溃疡40例[J].广西中医药,2002,25(1):29
    [27]康存战,向社干,陈虹,等.三七胃痛丸治疗消化性溃疡50例[J].中国中西医结合杂志,2003,23(11):870
    [28]王永华,邓美玲,王秀蕾,等.黄连清胃汤治疗十二指肠溃疡55例[J].中国民间疗法,2003,11(9):48
    [29]蒋映明.白拟复胃汤治疗消化性溃疡124例[J].广西中医药,2004,27(2):17
    [30]王丽英,田杰.胃肠溃疡散治疗消化性溃疡临床研究[J].河南中医,2002,22(3):34-35
    [31]要瑞莉,张连元,门秀丽.大鼠肢体缺血再灌注所致胃粘膜损伤及其机制[J].天津医学院学报,2004,8(4):448-449.
    [32]赵维中,岑德意,王瑜等.大剂量酮芬洛芬与吲哚美辛的致小鼠胃粘膜损伤作用[J].安徽医科大学学报,1994,34(2):27-29.
    [33]Guo FN,Chen GZ,Liu SQ.The effects of smoking and nicontine on the parietal cell mass of human beings and rats[J].Gastmenteral Hepatol,1986,1:45.
    [34]Mceready DR,Clak L,Cohen MM.Cigarette smoking reduces human gastric luminal prostaglandin E2[J].Gul,1985,26:1192.
    [35]Jarls LR,Whitehead R.Effect of nicontine on the morphology of the rat gastric muscosl[J].Gastroenterology,1978,78:1448.
    [36]王继德,周殿元,张万岱.幽门螺旋菌的致病机制[J].国外医学·消化系疾 病分册,1994,14(1):14-16.
    [37]张占海,杨丽彩,危北海等.建立萎缩性胃炎幽门螺旋杆菌感染动物模型的方法[J].中国中西医结合脾胃杂志,1996,4(1):46-47.
    [38]孙凤蓬,宋于刚,覃汉荣.胃溃疡大鼠胃泌素、生长抑素和GD细胞的变化[J].世 界华人消化杂志,2004,12(2):363-366.
    [39]陈作兴,陈晓琴,韦玉忠.吸入二异氰酸甲苯酯致大白兔肺、胃等脏器损害的病理观察[J].职业医学,1994,21(6):48.
    [40]张晓珠,常雅萍,于永利.梅花鹿免疫细胞活性因子对乙醇型胃粘膜损伤模型鼠的保护作用[J].中国生物制品学杂志,2003,16(1):39-40.
    [41]聂时南,李兆申,许国铭,等.躯体性及心理性应激状态下大鼠胃粘膜NOS活性与胃粘膜损伤[J].第二军医大学报,2000,21(1):1012.
    [42]赵敬国,李建文,王茂叶.运动应激性溃疡及其机制的实验研究[J].山东体育科技,2003,25(4):22-62.
    [43]蒋海清,侯奕,黄晓焰,等.辣椒治疗胃粘膜损伤及溃疡的实验与临床研究[J].赣南医学院学报,2003,23(4):369-370.
    [44]刘冬梅,幽门螺杆菌感染动物模型的研究进展[J].现代消化介入诊疗杂志,2000,5(2):64-67.
    [45]季忠国,朱人敏.胃黏膜屏障在消化性溃疡中作用的研究进展[J].现代消化介人诊疗杂志,2006,11(2):89-90.
    [46]夏锦军,黄桂勇,徐正新.胃溃宁胶囊药理实验研究[J].时珍国医国药,2000,11(1):11-12.
    [47]彭连生,胡锡元,曹淑亚,等.健胃口服液抗消化性溃疡的药理研究[J].中国中西医结合消化杂志,2001,9(3):150-152.
    [48]李岩,李永渝,崔瑞平.具钙通道阻滞剂活性的中药对消化性溃疡相关因素的研究[J].贵州医药,1998,22(6):469-471.
    [49]万清信,王燕,王德才.愈疡散治疗消化性溃疡的临床与实验研究[J].中国中西医结合杂志,1996,16(2):78-80.
    [50]陈芝芸,项柏康,朱林喜,等.100味中药对幽门螺旋杆菌抑菌作用的实验研究[J].时珍国医国药研究,1996,7(1):25-26.
    [51]张淑琴,刘慧敏,郭强,等.中药龙黄合剂对幽门螺旋杆菌治疗作用的实验观察[J].天津医药,1999,27(3):158-159.
    [52]李慧吉,武成,张世林.心身1号抗应激性溃疡的实验研究[J].中医杂志,1999,38(10):623-624.
    [53]王长洪,王艳红,周莹.中药对胃粘膜合成前列腺素的临床及实验研究[J].中国中西医结合杂志,1994,14(9);528-530.
    [54]黄玲.溃疡合剂的药理作用研究[J].现代中西医结合杂志,2000,9(6):471-472.
    [55]常青,李和泉,原泽茂.丹参抗消化性溃疡的机理探讨[J].中国病理生理杂志,1992,8(5):524.
    [56]王毓明,贾黎明,郑家驹,等.川芎嗪对胃粘膜血液量影响的实验及临床研究[J].江苏医药,2000,26(1):44-45.
    [57]郭蓉晓,王枢,易明娟,等.中药活血化瘀胶囊抗消化生溃疡的实验研究[J].华西药学杂志,1999,14(1):22-24.
    [58]程佳,迟晖.胃疡康治疗消化性溃疡的动物实验观察[J].中国病理生理杂志,1997,13(3):301-316.
    [59]梅武轩,邓兰琼,崔世高.柴胡桂枝汤对大鼠乙酸胃溃疡愈合质量的影响[J].中国中西医结合脾胃杂志,2000,8(5):278-280.
    [60]卜平,陈剂鸣,朱瑞锦.益气化瘀中药抗溃疡复发的临床与实验研究[J].南京中医药大学学报,1996,12(5):18-19.
    [61]甘爱萍,叶松.胃溃灵免疫调节作用的实验研究[J].新消化病学杂志,1996,4(3):125-127.
    [62]叶松,甘爱萍.胃溃灵对消化性溃疡患者免疫功能调节作用的探讨[J].中国中西医结合脾胃杂志,1997,5(2):80-83.
    [63]王庆国,李宇航,牛欣,等.半夏泻心汤及其拆方对慢性胃溃疡大鼠表皮生长因子的影响[J].中国中西医结合急救杂志,2001,8(3):731.
    [64]李长军,张蕙,王革革,等.消渍灵对消化性溃疡及萎缩性胃炎患者血清、胃液表皮生长因子含量的影响[J].新中医,2001,33(9):12-13.
    [65]张永锋,赵燕平,刘立昌,等.健胃汤抗大鼠乙酸胃溃疡及泼尼松再损伤的实验研究[J].中国中西医结合消化杂志,2002,10(2):86
    [66]陈绍斌,肖风仪,李国成.消溃疡灵对乙酸性胃溃疡大鼠内皮素及表皮生长因子受体的影响[J].浙江中西医结合杂志,2003,13(1):4.
    [67]魏岳斌.丹参对胃溃疡大鼠血清一氧化氮含量和胃粘膜表皮生长因子受体表达的影响[J].中国中西医结合消化杂志,2000,9(4):211-212.
    [68]郑学刚.胃痛宁对胃溃疡大鼠组织EGF及NO含量的影响研究[J].中医药学刊,2003,21(5):701-702.
    [69]郑学刚.胃痛宁对大鼠乙酸胃溃疡粘膜保护作用机制研究[J].湖北中医杂志,2003.25(6):7-8.
    [70]陈绍夫,潘丽丽,李岩,等.木香对犬的胃酸及血清胃泌素血浆生长抑素浓度的影响[J].中医药研究,1998,14(5):45-48.
    [71]陈绍斌,李国成,张连辉,等,消溃灵对乙酸性胃溃疡大鼠一氧化氮和内皮素的影响[J].中医药研究,1998,14(5):45-48.
    [72]贾公浮,等.简明中西医新用联用手册.长沙:湖南科技出版社,1998:168.
    [73]朱丽丽.金匮肾气丸治疗慢性肾炎26例临床观察[J].山西临床医药杂志,1998,7(5):332-333.
    [74]姚连初.肾气丸对原发肾病综合征患者外周血糖皮质激素受体水平的影响[J].中成药,2000,22(10):704-705.
    [75]潘晓明.肾气丸对男科疾病影响的研究概况[J].湖南中医学院学报,1994,14(2):61-64.
    [76]杨学信.金匮肾气丸加味治疗复发性泌尿系结石102例观察[J].四川中医,2003,21(9):51.
    [77]柳英华,孙琼.金匮肾气丸临床应用举隅[J].山东中医杂志,1994,13(7):305-306.
    [78]曹奕,姜英,张庆萍.金匮肾气丸治疗糖尿病肾病18例[J].陕西中医,1996,17(8):363.
    [79]陈可冀,李春生.岳美中教授用经方起大症之经验[J].新中医,1983,(4):8-12.
    [80]何清湖,郑毅春,李儇羽.金匮肾气丸治男性不育症临床观察[J].天津中医药,2003,20(1):18-19.
    [81]朱士伏.金匮肾气丸双向调节的临床应用[J].河南中医,1994,14(5):28.
    [82]卢承德.中西医结合治疗甲状腺功能减退症20例[J].陕西中医,1997,18(10):448-449
    [83]刘得华.金匮肾气丸治疗阴阳两虚型2型糖尿病62例临床观察口[J].新中医,2004,36(7):31-32.
    [84]马群力,王建华,吴素方,等.金匮肾气丸防治放疗辐射损伤30例观察[J].实用中医药杂志,2004,20(7):358.
    [85]刘瑞华,李维苹,王恒和.温。肾补阳法对慢性乙型肝炎患者外周围血T淋巴细胞亚群的影响[J].福建中医药,2000,31(4):14-15
    [86]黄闽杰,等.三联中成药口服治疗老年血管性痴呆[J].吉林中医药,2003,23(1):18.
    [87]孙振涛,等.金匮肾气丸合六味地黄丸加味治疗顽固性失眠[J].中国临床医生,2003,31(6):63.
    [88]刘宝炉.肾气丸治疗多发性硬化症验案1例[J].新中医,1997,29(7):52-53.
    [89]刘浙伟.金匮肾气丸为主改善老年人SOD、LPO等衰老指标的观察[J].新中医,1996,28(11):59-60.
    [90]白雨武.金匿肾气丸和左旋眯唑治疗支气管哮喘18例观察[J].实用中西医结合杂志,1991,4(7):426-427.
    [91]晋玉梅.金匮肾气丸治疗咳嗽的体会[J].河南中医药学刊,1997,12(4):39-40.
    [92]仝战旗,杨明会.金匮肾气丸在老年病中应用[J].陕西中医,1996,17(3): 132.
    [93]张益康,王诚喜.金匮肾气丸加减治疗冠心病不稳定型心绞痛40例疗效观察[J].新中医,2007,39(6):19-20.
    [94]汪少林,等.金匮肾气丸临床运用[J].甘肃中医学院学报,2002,19(3):35.
    [95]傅华洲,童燕玲,朱祥俊.金匮肾气丸治疗缓慢性心律失常60例临床观察[J].浙江中医杂志,1996,31(5):196-197.
    [96]张惠荣.金匮肾气丸治疗充血性心力衰竭体会[J].河北中医,1998,20(1):43.
    [97]何杭,何欣.金匮肾气丸治疗肠易激综台征50例[J].浙江中医杂志,1998,33(8):340.
    [98]汪连珍.金匮肾气丸治疗老年慢性功能性腹泻疗效观察[J].现代中西医结合杂志,2000,9(5):418-419.
    [99]林少辉,柳东杨,陈育忠,等.肾气丸治疗胃下垂64例疗效观察[J].新中医,2001,33(9):29.
    [100]寇建仁,等.金匮肾气丸复方治验[J].中医文献杂志,2003,21(1):54-55.
    [101]王小花.金匮肾气丸新用[J].黑龙江中医药,2000,(4):59.
    [102]李仁灿.金匮肾气丸治妇科杂病举隅[J].河南中医.1998,18(3):164
    [103]王清华,韩小芳,张敏秀.金匮肾气丸加减治疗产后尿潴留2例[J].中西医结合杂志,1988,(7):445.
    [104]王悦芳,朱戚龙.张桂英.金匮肾气丸治疗静脉血栓形成[J].中医药信息,1996,13(5):32.
    [105]大萱谂,等.国外医学·中国中药分册,1994,16(3):31.
    [106]杨功旭.金匮肾气丸为主治疗腰椎间盘突出症15例[J].湖北中医杂志,1997.19(2):18.
    [107]陈松林.金匮肾气丸治疗骨折延期愈合30例疗效观察[J].河南中医药学刊,2002,17(6):51-52.
    [108]虞孝萼.金匮肾气丸新用[J].安徽中医学院学报,1999,18(6):40.
    [109]钟铁锋,张翼翔.金匮肾气丸治疗急性痛风33体会[J].按摩与导引,1998,14(1):47.
    [110]罗道揆.金匮肾气丸加味治疗小儿夏季热[J].上海中医药杂志,1991,(6):19.
    [111]卢普纯,戴陆庆.金匮肾气丸加减治疗复发性口疮64例[J].赣南医学院学报,1997,17(3):254.
    [112]王跃进,杨爽,何建华.金匮肾气丸治疗中心性浆液性脉络膜视网膜病变[J].河南中医,2003,23(1):16-17.
    [113]路新国.金匮肾气丸治疗寒冷性荨麻疹[J].上海中医药杂志,1988,(9):32-34.
    [114]刘金耀,周平.用金匮肾气丸治疗2例冷球蛋白血症[J].中华皮肤科杂志,1988,21(3):168-169.
    [115]岛津孝.用小动物检定糖尿病治疗药的方法及八味地黄丸的效果[J].国外医学·中医中药分册.1984,6(1):56-57.
    [116]余美娟,姚晓喻,周思萍,等.金匮肾气丸对鹌鹑食饵性高脂血症和血清过氧化脂质的影响[J].中国药学杂志,1990,25(7):410-412.
    [117]小曾户洋.八味地黄丸对加龄的影响-八味地黄丸与谷胱甘肽代谢[J].国外医学·中医中药分册,1984,6(1):57-58.
    [118]王东方,等.金匮肾气丸拮抗庆大霉素耳毒性作用的机理研究[J].南京中医药大学学报,1997,13(5):284-286.
    [119]袁世宏,等.金匮肾气丸对“恐伤'肾”大鼠丘脑、海马c-fos基因表达的影响[J].北京中医药大学学报,2001,24(6):34-36.
    [120]张莹雯,等.金匮肾气丸对老年雌性大鼠一氧化氮、性激素的影响[J].中成药,2003,25(3):252-253.
    [121]周坤福,等.金匮肾气丸延缓衰老作用的实验研究[J].南京中医药大学学报,1998,14(6):351-352.
    [122]张玉芳,等.加味肾气丸药理作用的研究[J].中成药,1996,18(7):25-26.
    [123]蒋珠芬,田军,杨士友,等.桂附地黄口服液的药理作用[J].中成药,1991,13(11):46.
    [124]夏蓉西,刘红潮,李海忠,等.肾气丸恢复受损睾丸功能的实验研究[J].中成药,1993,15(11):25-26.
    [125]张柏丽,等.肾气丸对大鼠睾丸组织内DNA和RNA含量的影响[J].天津中医,1995,12(4):30.
    [126]李震,等.应用诱导劳倦过度、房事不节法建立肾阳虚模型的研究[J].山东中医学院学报,1994,18(6):418-419.
    [127]李震,等.应用诱导“劳倦过度、房室不节”法建立肾虚模型的研究[J].实用中西医结合杂志,1995,8(8):585-586.
    [128]刘红潮,等.肾气丸对幼龄雄性大鼠生殖系统的影响[J].天津中医,1997,14(6):270-271.
    [129]马红,等.金匮肾气丸免疫调节作用的实验研究[J].中药药理与临床,2000,16(6):5-6.
    [130]冯璞,等.金匮肾气丸对免疫缺陷小鼠免疫造血功能的影响[J].中药药理与临床,1998,14(1):9-11.
    [131]周联.肾阳虚大鼠免疫器官环核苷酸改变及肾气汤对其影响[J].广州中医学 院学报,1992,9(2):76-78.
    [132]王培训,等.补肾健脾方药免疫药理作用比较[J].中药新药与临床药理,1998,9(2):84-86.
    [133]徐文流,等.肾虚与脾虚模型动物IL-1的比较[J].广州中医药大学学报,1997,14(3):175-177.
    [134]王学礼,等.金匮肾气丸对家兔实验性骨折后骨痂生长的影响[J].实用中西医结合杂志,1991,1(11):683-684.
    [135]石印玉,等.补肾中药防治原发性骨质疏松症的细胞学研究[J].中医杂志,2001,42(10):621-623.
    [136]郑小伟,刘明哲,程志清,等.金匮肾气丸对SD大鼠慢性电离辐射损伤的防护作用[J].中国中医药科技,1999,6(6):382.
    [137]郑小伟,等.金匮肾气丸对带瘤小鼠辐射损伤的保护作用[J].中国医药学报,1999,14(1):73-74.
    [138]张建新,李兰芳,吴树勋,等.八味地黄丸口服液药理作用研究[J].中成药,1994,16(3):32-33.
    [139]王明艳,吴海涛,赵鸣芳,等.4种方药对环磷酰胺诱发的SCE的抑制作用[J].中成药,2000,22(3):212-214.
    [140]中国科学院西北高原生物研究所藏药志.青海人民出版社,1991,248.
    [141]青海省药品柱验所、青海省藏医药研究所.中国藏药.上海:科学技术出版社.1996,343.
    [142]江苏新医学院中药大辞典(上册).上海;科学技术出版社.1986,436.
    [143]周平,李和泉.丹参提取物F对大鼠乙酸-消炎痛胃溃疡愈合的影响[J].中国病理生理杂志,1997,13(5):479-482.
    [144]Yanaka A,Suzuki H,Shibahara,et al.EGF promotes gastric restitution by activating Na/H exchange of epithelial cells[J].Am J Physiol Gastrointest Liver Physiol,2002,282(5):866.
    [145]Milani s,Calabro A.Role of growth factors and the irmeeptors in gastric ulcer healing[J].Microsc Res Tech,2001,53(5):360.
    [146]唐志鹏,许鑫梅,叶柳忠,等.健中愈疡片对乙酸诱导胃溃疡大鼠表皮生长因子及其受体表达的影响[J].中国中西医结合消化杂志,2006,4(2):99.
    [147]王长洪.前列腺素与胃粘膜.中国中西医结合脾胃杂志,1995,3(1):51.
    [148]林庚金.消化病学新概念.第10版.上海;上海医科大学出版社,1997.31.
    [149]杨院平.一氧化氮与内皮素在胃黏膜损伤中的作用与关系[J].陕西医学杂志,2002,31(2):137-140.
    [150]MASUDA E,KAW ANO S,MICHIDA T,et al.Plasma and gastric mucosal endothelin-1 concentration in patients with peptic ulcer[J].Dig D Sci,1997,42(2):314-318.
    [151]KAWAMP S,TSUJ IS.Role of mucosal blood flow:a conceptional review in gastric mucosal injury and protection[J].J Gastroenterol Hepatol,2000,15(Suppl):D1-D6.
    [152]张在兴.胃粘膜内源性保护因子研究进展.国外医学消化系统疾病分册.1997,17:201.
    [153]Yanagisawa M,Kufihara H,Kimura S.A novel potent vasoconstrictor prptide by Vascular endothelial ceUs.Nuture.1988,332(6163):411.
    [154]李国成,陶秀良,罗树星.一氧化氮与慢性胃溃疡关系的实验研究.同济医科大学学报.2000,29:177.

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