和中消溃汤对乙酸溃疡模型大鼠胃粘膜保护作用的研究
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摘要
目的:
研究和中消溃汤对乙酸溃疡模型大鼠胃粘膜的保护作用,探讨其发挥保护作用促进溃疡愈合的作用机制,为中医药治疗胃溃疡提供实验依据。
方法:
在质量为200-250g的70只健康成年雄性大鼠中随机抽取10只作为正常空白对照组,余下60只均用乙酸烧灼法造模:在腺胃部腹面胃体与幽门窦交界处的浆膜下近肌层处注射100%乙酸液体30μl,形成直径约3mm白色小丘,造模后第4天在造模60只大鼠中随机抽取10只大鼠剖腹取胃观察溃疡形成情况,判断造模效果,以成功率>80%时,认为造模成功。余下50只大鼠随机分为5组,加上先前正常空白对照组,共6组:正常空白对照组、模型组、和中消溃汤大剂量组、和中消溃汤中剂量组、和中消溃汤小剂量组、丽珠得乐组,造模第5天用大剂量(25.2g/Kg*d),中剂量(12.6g/Kg*d),小剂量(6.3g/Kg*d)和中消溃汤、丽珠得乐(0.36g/Kg*d)分别给用药组大鼠灌胃,正常空白对照组、模型组给以生理盐水。持续灌胃16天,1次/天。16天后处死大鼠,断头取血,测量血浆ET含量;剖腹取胃,取溃疡组织切片、分别作HE染色及PAS染色以观察灌胃后各模型组大鼠的溃疡愈合情况,用显微镜测微尺定量测量胃再生粘膜厚度;取溃疡边缘胃组织匀浆后测NO、MDA、SOD含量,取腺胃组织匀浆后测EGF、6-Keto-PGF_1a含量,比较各组间差异,用SPSS统计软件处理分析数据。
结果:
1.对乙酸溃疡模型大鼠胃再生粘膜厚度的影响:和中消溃汤大剂量组、中剂量组、小剂量组和丽珠得乐组大鼠再生粘膜厚度均明显高于模型组(P<0.05～0.01);和中消溃汤大剂量组明显高于丽珠得乐组(P<0.05),丽珠得乐组与和中消溃汤中剂量组之间无显著性差异(P>0.05),和中消溃汤在增加再生粘膜厚度方面,各剂量组之间存在量效关系。
2、对乙酸溃疡模型大鼠胃组织一氧化氮(NO)及超氧化物歧化酶(SOD)含量的影响:和中消溃汤大剂量组、中剂量组、小剂量组大鼠胃组织NO及SOD的含量明显高于模型组与丽珠得乐组(P<0.05或P<0.01),丽珠得乐组与模型组之间上述指标无显著性差异(P>0.05),和中消溃汤大剂量组与正常组之间无显著性差异(P>0.05),和中消溃汤在增加大鼠胃组织NO及SOD方面各剂量组之间存在量效关系。
3.对乙酸溃疡型大鼠血浆内皮素(ET)和胃组织丙二醛(MDA)含量的影响:和中消溃汤大、中、小剂量组大鼠血浆ET和胃组织MDA含量明显低于模型组与丽珠得乐组(P<0.01或P<0.05),丽珠得乐组与模型组之间上述指标无显著性差异(P>0.05),和中消溃汤大剂量组与正常组之间无显著性差异(P>0.05),和中消溃汤在减少血浆ET和胃组织MDA含量方面各剂量组之间存在量效关系。
4.对乙酸溃疡型大鼠胃组织表皮生长因子(EGF)和6-酮-前列腺素F_1a(6-Keto-PGF_1a)含量的影响:和中消溃汤大、中、小剂量组,丽珠得乐组大鼠胃组织表皮生长因子(EGF)和6-酮-前列腺素F_1a(6-Keto-PGF_1a)含量明显高于于模型组(P<0.01),丽珠得乐组表皮生长因子(EGF)含量略高于和中消溃汤大剂量组,差别无显著性意义(P>0.05)。但丽珠得乐组6-酮-前列腺素F_1a(6-Keto-PGF_1a)含量明显高于和中消溃汤大剂量组(P<0.05),和中消溃汤在减少血浆ET和胃组织MDA含量方面各剂量组之间存在量效关系。
结论:
和中消溃汤能显著增加乙酸溃疡模型大鼠胃再生粘膜厚度以促进溃疡愈合,其作用优于丽珠得乐,呈剂量依赖性关系。其作用机理可能与其增加胃组织EGF、SOD、NO、6-Keto-PGF_1a含量和减少MDA、血浆ET含量有关,增强胃粘膜的保护作用是和中消溃汤治疗胃溃疡的机制之一。此实验说明了和中消溃汤组方用药的合理性和科学性,对于指导临床治疗胃溃疡中医用药以及开发新药等,都具有一定的参考价值。
Objective:To investigate the protective effect of Hezhongxiaokui decoction on gastric mucosa of rats with ulcer induced byAcetic Acid.To study its therapeutic effect as well as the possible mechanism.And to provide a clinical rationale for treatment of gastric ulcer.
Methods:10 of 70 male healthy adult rats from quality,range 200—250g,were choosed to form the normal control group at random. The others were all induced chronic gastric ulcer by Acetic Acid,(inject 30μl 100%Acetic Acid at the Subserosa of juncture of the ventral aspect corpus gastricum of stomachus glandularis and gastric antrum to form a white nodule with approxinate diameter of 3mm ).At the 4th day after modiing 10 rats were choosed to evaluate whether the modle was successful.If success rates was greater than 80%,successful modle was seen established.The left 50 rats were devided into 5 groups at random:Model group、high dose group of Hezhongxiaokui decoction(25.2g/Kg*d)、medium dose group of Hezhongxiaokui decoction(12.6g/Kg*d)、low dose group of Hezhongxiaokui decoction(6.3g/Kg*d)、Lizhu Dele group(0.36g/Kg*d). Rats of Hezhong Xiaokui decoction group and Lizhu Dele group were intragastric administrated Hezhong Xiaokui Physic liquors and Lizhu Dele Physic liquors respectively,one time per day,totally 16 days.The others were intragastric administratednormal saline. 16 days later,All the rats were executed to collect blood to detect the content of Plasma ET,and rats' s belly were cut open and removed the stomach to slice the scar of ulcer tissue.After HE dyeing and PAS dyeing separately we observed the healing condition of the ulce,r and measured the thickness of regenerative mucosa,Meanwhile, we detect the content of NO、MDA、SOD、EGF、6-Keto-PGF,a of stomach tissue.At last we compared the difference of interclass and analyzed data by SPSS statistics software.
Results:
1.The determination the thickness of theregeneratice mucosa on chronic gastric ulcer rats has showed that compared with model group, the thickness of gastric mucosa increased significantly in each dose of Hezhong Xiaokui group and Lizhu Dele group(P<0.05-0.01), High dose group of Hezhongxiaokui decoction had muchthicker regeneratice mucosa than Lizhu Dele group,and there was remarkable difference between the high dose group and the LizhuDelegroup (P<0.05).and there was no significant difference between the high dose group and the normal control group(P>0.05).On increasing the thickness of the regeneratice mucosa on chronic gastric ulcer rats there's a dose-dependent effect in the result.
2.The determination of the content of SOD and NO has showed that the content of SOD and NO of each dose group of Hezhongxiaokui decoction is much higher than that of LizhuDele and model group,and there was remarkable difference betweenhigh、medium、low dose group and LizhuDele group and model group(P<0.05-0.01).There was no significant difference between normal group and high dose group as well as the model group and LizhuDele group(P>0.05).On increasing the content of SOD and NO,there's a dose-dependent effect in the result.
3.The determination of the content of ET and MDA has showed that the content of ET and MDA of each dose group of Hezhongxiaokui decoction is much lower than that of LizhuDele and model group, there was remarkable difference betweenhigh、medium、low dose group and LizhuDele group and model group(R<0.05-0.01).There was no significant difference between normal control group and high dose group as well as the model group and LizhuDele group(P>0.05). On decreasing the content of SOD and NO?there's a dose-dependent effect in the result.
4.The determination of the content of EGF and 6-Keto-PGF_1a has showed that the content of EGF and 6-Keto-PGF_1a of each dose group of Hezhongxiaokui decoction and LizhuDele group is much higher than that of model group,and the content of 6-Keto-PGF_1a of LizhuDele group is much higher than that of each dose group of Hezhongxiaokui decoction(P<0.01).while the EGF a little higher(P>0.05).On increasing the content of SOD and NO,there' s a dose-dependent effect in the result.
Conclusions:Hezhongxiaokui decoction can pronote the growth of the regeneratice mucosa on rats to accelerate the ulcer healing up and the effect was better thanLizhu Dele.the effect in the result was dose-dependent.It might be due to improvement of the the level of SOD、NO、EGF、6-Keto-PGF_1a and its decrease of the ET and MDA levels.Enhancing the protective effect on gastric mucosa was one of possible mechanisms on Hezhongxiaokui decoction treating gastric ulcer.The study provide a reference data for understanding the mechanism of this therapeutic method.Meanwhile,it is valuable for guiding the clinical practice in treating gastric ulcer and development of new medication.
研究和中消溃汤对乙酸溃疡模型大鼠胃粘膜的保护作用,探讨其发挥保护作用促进溃疡愈合的作用机制,为中医药治疗胃溃疡提供实验依据。
方法:
在质量为200-250g的70只健康成年雄性大鼠中随机抽取10只作为正常空白对照组,余下60只均用乙酸烧灼法造模:在腺胃部腹面胃体与幽门窦交界处的浆膜下近肌层处注射100%乙酸液体30μl,形成直径约3mm白色小丘,造模后第4天在造模60只大鼠中随机抽取10只大鼠剖腹取胃观察溃疡形成情况,判断造模效果,以成功率>80%时,认为造模成功。余下50只大鼠随机分为5组,加上先前正常空白对照组,共6组:正常空白对照组、模型组、和中消溃汤大剂量组、和中消溃汤中剂量组、和中消溃汤小剂量组、丽珠得乐组,造模第5天用大剂量(25.2g/Kg*d),中剂量(12.6g/Kg*d),小剂量(6.3g/Kg*d)和中消溃汤、丽珠得乐(0.36g/Kg*d)分别给用药组大鼠灌胃,正常空白对照组、模型组给以生理盐水。持续灌胃16天,1次/天。16天后处死大鼠,断头取血,测量血浆ET含量;剖腹取胃,取溃疡组织切片、分别作HE染色及PAS染色以观察灌胃后各模型组大鼠的溃疡愈合情况,用显微镜测微尺定量测量胃再生粘膜厚度;取溃疡边缘胃组织匀浆后测NO、MDA、SOD含量,取腺胃组织匀浆后测EGF、6-Keto-PGF_1a含量,比较各组间差异,用SPSS统计软件处理分析数据。
结果:
1.对乙酸溃疡模型大鼠胃再生粘膜厚度的影响:和中消溃汤大剂量组、中剂量组、小剂量组和丽珠得乐组大鼠再生粘膜厚度均明显高于模型组(P<0.05～0.01);和中消溃汤大剂量组明显高于丽珠得乐组(P<0.05),丽珠得乐组与和中消溃汤中剂量组之间无显著性差异(P>0.05),和中消溃汤在增加再生粘膜厚度方面,各剂量组之间存在量效关系。
2、对乙酸溃疡模型大鼠胃组织一氧化氮(NO)及超氧化物歧化酶(SOD)含量的影响:和中消溃汤大剂量组、中剂量组、小剂量组大鼠胃组织NO及SOD的含量明显高于模型组与丽珠得乐组(P<0.05或P<0.01),丽珠得乐组与模型组之间上述指标无显著性差异(P>0.05),和中消溃汤大剂量组与正常组之间无显著性差异(P>0.05),和中消溃汤在增加大鼠胃组织NO及SOD方面各剂量组之间存在量效关系。
3.对乙酸溃疡型大鼠血浆内皮素(ET)和胃组织丙二醛(MDA)含量的影响:和中消溃汤大、中、小剂量组大鼠血浆ET和胃组织MDA含量明显低于模型组与丽珠得乐组(P<0.01或P<0.05),丽珠得乐组与模型组之间上述指标无显著性差异(P>0.05),和中消溃汤大剂量组与正常组之间无显著性差异(P>0.05),和中消溃汤在减少血浆ET和胃组织MDA含量方面各剂量组之间存在量效关系。
4.对乙酸溃疡型大鼠胃组织表皮生长因子(EGF)和6-酮-前列腺素F_1a(6-Keto-PGF_1a)含量的影响:和中消溃汤大、中、小剂量组,丽珠得乐组大鼠胃组织表皮生长因子(EGF)和6-酮-前列腺素F_1a(6-Keto-PGF_1a)含量明显高于于模型组(P<0.01),丽珠得乐组表皮生长因子(EGF)含量略高于和中消溃汤大剂量组,差别无显著性意义(P>0.05)。但丽珠得乐组6-酮-前列腺素F_1a(6-Keto-PGF_1a)含量明显高于和中消溃汤大剂量组(P<0.05),和中消溃汤在减少血浆ET和胃组织MDA含量方面各剂量组之间存在量效关系。
结论:
和中消溃汤能显著增加乙酸溃疡模型大鼠胃再生粘膜厚度以促进溃疡愈合,其作用优于丽珠得乐,呈剂量依赖性关系。其作用机理可能与其增加胃组织EGF、SOD、NO、6-Keto-PGF_1a含量和减少MDA、血浆ET含量有关,增强胃粘膜的保护作用是和中消溃汤治疗胃溃疡的机制之一。此实验说明了和中消溃汤组方用药的合理性和科学性,对于指导临床治疗胃溃疡中医用药以及开发新药等,都具有一定的参考价值。
Objective:To investigate the protective effect of Hezhongxiaokui decoction on gastric mucosa of rats with ulcer induced byAcetic Acid.To study its therapeutic effect as well as the possible mechanism.And to provide a clinical rationale for treatment of gastric ulcer.
Methods:10 of 70 male healthy adult rats from quality,range 200—250g,were choosed to form the normal control group at random. The others were all induced chronic gastric ulcer by Acetic Acid,(inject 30μl 100%Acetic Acid at the Subserosa of juncture of the ventral aspect corpus gastricum of stomachus glandularis and gastric antrum to form a white nodule with approxinate diameter of 3mm ).At the 4th day after modiing 10 rats were choosed to evaluate whether the modle was successful.If success rates was greater than 80%,successful modle was seen established.The left 50 rats were devided into 5 groups at random:Model group、high dose group of Hezhongxiaokui decoction(25.2g/Kg*d)、medium dose group of Hezhongxiaokui decoction(12.6g/Kg*d)、low dose group of Hezhongxiaokui decoction(6.3g/Kg*d)、Lizhu Dele group(0.36g/Kg*d). Rats of Hezhong Xiaokui decoction group and Lizhu Dele group were intragastric administrated Hezhong Xiaokui Physic liquors and Lizhu Dele Physic liquors respectively,one time per day,totally 16 days.The others were intragastric administratednormal saline. 16 days later,All the rats were executed to collect blood to detect the content of Plasma ET,and rats' s belly were cut open and removed the stomach to slice the scar of ulcer tissue.After HE dyeing and PAS dyeing separately we observed the healing condition of the ulce,r and measured the thickness of regenerative mucosa,Meanwhile, we detect the content of NO、MDA、SOD、EGF、6-Keto-PGF,a of stomach tissue.At last we compared the difference of interclass and analyzed data by SPSS statistics software.
Results:
1.The determination the thickness of theregeneratice mucosa on chronic gastric ulcer rats has showed that compared with model group, the thickness of gastric mucosa increased significantly in each dose of Hezhong Xiaokui group and Lizhu Dele group(P<0.05-0.01), High dose group of Hezhongxiaokui decoction had muchthicker regeneratice mucosa than Lizhu Dele group,and there was remarkable difference between the high dose group and the LizhuDelegroup (P<0.05).and there was no significant difference between the high dose group and the normal control group(P>0.05).On increasing the thickness of the regeneratice mucosa on chronic gastric ulcer rats there's a dose-dependent effect in the result.
2.The determination of the content of SOD and NO has showed that the content of SOD and NO of each dose group of Hezhongxiaokui decoction is much higher than that of LizhuDele and model group,and there was remarkable difference betweenhigh、medium、low dose group and LizhuDele group and model group(P<0.05-0.01).There was no significant difference between normal group and high dose group as well as the model group and LizhuDele group(P>0.05).On increasing the content of SOD and NO,there's a dose-dependent effect in the result.
3.The determination of the content of ET and MDA has showed that the content of ET and MDA of each dose group of Hezhongxiaokui decoction is much lower than that of LizhuDele and model group, there was remarkable difference betweenhigh、medium、low dose group and LizhuDele group and model group(R<0.05-0.01).There was no significant difference between normal control group and high dose group as well as the model group and LizhuDele group(P>0.05). On decreasing the content of SOD and NO?there's a dose-dependent effect in the result.
4.The determination of the content of EGF and 6-Keto-PGF_1a has showed that the content of EGF and 6-Keto-PGF_1a of each dose group of Hezhongxiaokui decoction and LizhuDele group is much higher than that of model group,and the content of 6-Keto-PGF_1a of LizhuDele group is much higher than that of each dose group of Hezhongxiaokui decoction(P<0.01).while the EGF a little higher(P>0.05).On increasing the content of SOD and NO,there' s a dose-dependent effect in the result.
Conclusions:Hezhongxiaokui decoction can pronote the growth of the regeneratice mucosa on rats to accelerate the ulcer healing up and the effect was better thanLizhu Dele.the effect in the result was dose-dependent.It might be due to improvement of the the level of SOD、NO、EGF、6-Keto-PGF_1a and its decrease of the ET and MDA levels.Enhancing the protective effect on gastric mucosa was one of possible mechanisms on Hezhongxiaokui decoction treating gastric ulcer.The study provide a reference data for understanding the mechanism of this therapeutic method.Meanwhile,it is valuable for guiding the clinical practice in treating gastric ulcer and development of new medication.
引文
[1]胡伏莲.消化性溃疡发病机制的现代理念[J].中华消化杂志,2005,25(3):189-190.
[2]王苑本.消化性溃疡研究现状[J].新消化病杂志,1996,4(3):223.
[3]房殿春,彭志红.胃粘膜屏障功能研究概况(综述)[J].现代消化介入及治疗,2007,12(1):48-52.
[4]王崇文.消化性溃疡的抗幽门螺杆菌与抑酸维持治疗(述评)[J].中华消化杂志,2002,22(2):69-71.
[5]戴高中.论中医药治疗消化性溃疡的地位及优势[J].中国中西医结合消化杂志,2007,15(1):60-61.
[6]李艳,杨拯,王丽梅,等.消化性溃疡动物模型的研究进展[J].西南军医,2007,9(5):83-86.
[7]OkbaeS,AmagaseK.An ovevriew of acetic acidulcer models-the history and State of the art PePtic ulcer research[J].Biol Pharm Bull.2005,28(8):1321-1341.
[8]叶震世,任建林.胃粘液屏障与胃粘膜保护的研究进展[J].世界华人消化杂志,2005,13(21):2578-2581.
[9]李兆申主编.胃粘膜损伤与保护-基础与临床[M].第1版.上海:科技出版社,2004:69-87.
[10]Wallace JL,Granger DN.The cellular and molecular basis of gastric mucosal defense[J].FASEB J,2006;10(7):731-740.
[11]姒健敏.关注生长因子对胃粘膜的保护作用[J].中华医学杂志,2005,8(5):2744-2745.
[12]高娜.黄芪调节免疫功能的研究[J].长春中医药大学学报,2008,24(6):671.
[13]焦红军.党参的药理作用及其临床应用[J].临床医学.2005,25(4):92-93.
[14]吴丽芹,姜惟,顾武军,等.半夏泻心汤对慢性胃炎合并Hp感染大 鼠胃粘液层磷脂氨基已糖的影响[J].中医药研究,2001,17(1):41.
[15]郭一峰,周文丽,张建鹏,等.海螵蛸多糖对小鼠胃粘膜保护作用的研究[J].第二军医大学学报,2008,29(11):1328-1333.
[16]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,2002,8(5):524.
[17]韩广轩,孙义华,罗晓静.中药白及药理作用及临床应用进展[J].药学实践杂志,2004,22(4):24-26.
[18]于辉,李春香,宫凌寿,等.甘草的药理作用概述[J].现代生物医学进展,2006,6(4):77-80.
[19]Kalia N,Brown N J,Jacob S,et al.Studies on gastric mucosal microcirculation.1.The nature of regional variations indiced by ethanol injury[J].Gut,2000,40(1):31-35.
[20]梅武轩,邓兰琼.柴胡桂枝汤对大鼠胃溃疡愈合质量的影响[J].咸宁医学院学报,2000,14(3):172-175.
[21]张学智,周永芬.加味六君子汤治疗合并出血后的上消化道溃疡[J].陕西中医,2000,29(1):2.
[22]刘建平,胡冬菊,宗全和,等.健脾化瘀中药对大鼠胃溃疡愈合质量的影响[J].中国中西医结合杂志,2004,24(7):635-637.
[23]李松华,连超.胃粘液与胃粘膜保护的研究进展.国外医学消化疾病分册2002,22:1-3.
[24]李春艳,刘丽娜,等.一氧化氮与氧自由基在大鼠急性乙醇性胃粘膜损伤中的作用[J].中国病理生理杂志,2004,20(10):1777.
[25]陈绍斌,李国成.乙酸性胃溃疡大鼠一氧化氮、内皮素及表皮生长因子受体相互关系研究[J].中国中西医结合消化杂志,2002,10(5):259-262.
[26]施华秀,任建林.氧自由基与胃粘膜损伤[J].世界华人消化杂志,2005,13(21):2582-2585.
[27]韦维,林寿宁,黄贵华,等.安胃汤对胃溃疡大鼠溃疡修复及表皮生 长因子的影响[J].湖南中医药大学学报,2008,28(6):38-41.
[28]向华,侯小华.胃粘膜保护机制的研究[J].临床消化病杂志,2004,16(2):79-81.
[29]Kusterer K,Buchheit KH,Schade A,Bruns C,Neuberger C,Engel G,Msadel KH.The somatostatin analogue octreotide protects against ethanol-induced microcirculatory stasis and elevated vascular permeability in rat gastric mucosa[J].Eur J Pharmacol 2004;259(5):265-271.
[30]刘劲松,侯晓华.一氧化氮对胃粘膜保护机制的实验研究[J].华中科技大学学报,2004,33(5):592-593.
[31]Heung Mook Shin,全小林.加味参苓白术散对吲哚美辛所致大鼠胃粘膜损伤的保护作用[J].国外医学.中医中药分册,2000,22(5):279.
[32]许春娣.表皮生长因子在消化性溃疡愈合中的作用[J].国外医学儿科学分册2000,24(3):123-124.
[33]时昭红,张介眉,周慧芳,等.促愈颗粒对胃溃疡实验大鼠胃粘膜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,2007,15(1):25-27.
[34]Konturek L,Takeuchi K,Tarnawski A.Gastric mucosal defense and cytoprotection:bench to bedside[J].Gastroenterology.2008 Jul;135(1):41-60.
[35]Lee H,Hansson HA,Norstrom E,et al.Immunoreactivities for epidermal growth factor(EGF) and for EGF receptors in rats with gastric ulcers.Cell Tissue Res,1991,265(2):211-218.
[36]Tarnawski A,Stachura J,Durbin T,et al.Increased expression of epidermal growth factor receptor diring gastric ulcer healing in rats.Gastroenterology.1992 Feb;102(2):695-698.
[37]李长军,张蕙,王革革,等.消溃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.
[38]Dajani E.Is peptic ulcer a prostaglandin deficiency disease?[J].Hum Pathol,1998,17(2):106-107.
[39]Feldman M.Southwestern internal medicine conference:prostaglandins and gastriculcers:From seminal versicle tomisoprostol (Cytotect).Am J Med Sci,1999,300(7):116-118.
[40]Hinsdale JG,Engel JJ,Wilson DE.Prostaglandin E in peptic ulcer disease.Prostaglandins,2001,6(4):495-497.
[41]石以方,洪向秀,尚炽昌,等.加味黄连汤对大鼠慢性胃粘膜损伤PGE_2的影响及病理组织学改变[J].河南中医,2000,20(5):25.
[42]张秋霞,郭淑杰.四逆陷胸汤合方对实验大鼠慢性萎缩性胃炎血清胃泌素、胃粘膜PGE_2的影响[J].北京中医,2001,20(1):37-39.
[43]方尔笠,许宏俐,薛德彬,等.益气化瘀煎剂抗大鼠胃溃疡作用及其机制的探讨[J].中国中西医结合消化杂志,2001,9(4):208-209.
[44]汪建英,李振甲.6-keto-PGE_2和TXB在胃粘膜适应性细胞保护中的作用[J].生理学报,1986,38(5):451-452.
[45]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,2005,14(1):22-24.
[46]姜少芳.中医药治疗消化性溃疡概况[J].河北中医,2007,29(5):463-464.
[47]李冀.中医药治疗消化性溃疡研究进展[J].中医药学刊,2006,24(2):19-21.
[48]叶松,黄鹤,曹芳,等.中药治疗消化性溃疡实验研究进展[J].湖北中医杂志,2004,26(6):56-57.
[49]杨卫文,黎莉,邓亚杰,等.丹参治疗消化性溃疡的疗效及机制探讨[J].中华消化杂志,2002,22(7):438-439.
[1]张绍先.中西医结合治疗消化性溃疡60例疗效观察[J].云南中医杂志,2005,26(3):9-10.
[2]彭世敏.辨证治疗消化性溃疡79例[J].实用中医药杂志,2005,21(4):206-207.
[3]周仲瑛.中医内科学[M].第七版.北京:中国中医药出版社,2004:196.
[4]吴恒中,吴全明.胃脘痛中医辨证与幽门螺旋菌检测的关系初探[J].辽宁中医杂志,2003,11(5):14-17.
[5]李乾构.健胃愈疡片治疗消化性溃疡791例[J].中国中西医结合消化杂志,2004,12(5):291-293.
[6]田养年.胃肠疾病辨治验案4则[J].江苏中医药,2007,39(6):51-52.
[7]林孔孝,李克强.中西医结合治疗消化性溃疡78例[J].浙江中西医结合杂志,2004,5(12):748-749.
[8]罗关靖.中医辨证治疗消化性溃疡98例临床观察[J].河南中医,2003,23(2):29-30.
[9]于世杰.中医辨证治疗消化性溃疡45例[J].辽宁中医杂志,2003,39(5):382-383.
[10]彭连生,胡锡元,金李田,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):150-153.
[11]夏锦军,黄桂勇.胃溃宁胶囊药理实验研究[J].时珍国医国药,2000,11(1):11-12.
[12]李岩,向丽华.黄连药理作用及临床应用[J].甘肃中医,2004,17(12):5-7.
[13]万清信.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):78-81.
[14]陈芝芸,项柏康,朱林喜,等.100味中药对幽门螺旋杆菌和作用的试验研究[J].时珍国医国药研究,1996,7(1):25-26.
[15]乔雪枫,张淑琴.中西医结合治疗与幽门螺旋杆菌(HP)相关的消化性溃疡24例疗效观察[J].中华实用中西医杂志,2004,4(17):3243.
[16]许艺,叶柏,单兆伟,等.中草药单味与复方对幽门菌抑制作用研究[J].中国中西医结合脾胃杂志,2000,8(5):292-293.
[17]宋希仁,焦丛海.大黄治疗幽门弯曲菌阳性的消化性溃疡临床观察 [J].中医杂志,1991,32(5):25-27.
[18]黄玲,易受乡,刘雨姬,等.中医药对胃粘膜损伤保护作用机理研究进展[J].中国中医药信息杂志,2003,10(12):76-78.
[19]王国中,茹新,丁丽华,等.丹参抗大鼠乙酸胃溃疡和防止复发的效果[J].华人消化杂志,2003,6(1):38-39.
[20]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,2002,8(5):524.
[21]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,2005,14(1):22-24.
[22]王毓明,李明诊.川芎嗪对家兔胃粘膜“血流量”影响的实验研究[J].辽宁中医杂志,2002,26(12):565.
[23]唐梅文,王庆高,武青,等.溃疡疡愈合质量的影响因素与中医药干预的研究进展[J].广西中医药,2004,27(3):7-9.
[24]Kμsterer K,Pihan G,Seabo S.Role of lipid peroxidation in gastric mucosal lesion induced by HCL,NAOH or ischemia[J].Am J Physiol,2004,252(15):811-812.
[25]Atμma C,Engstrand L,Holm L.Extracts of Helicobacter pylori reduce gastric mucosal blood flow through a VacA-and CagA-independent pathway in rats[J].Scand J Gastroenterol,2002,33(12):1256-1258.
[26]Heμng Mook Shin,全小林.加味参苓白术散对吲哚美辛所致大鼠胃粘膜损伤的保护作用[J].国外医学·中医中药分册,2000,22(5):279-281.
[27]李长军,李国成,叶四平,等.消费灵治疗消化性溃疡的临床研究[J].中国中西医结合脾胃杂志,2001,9(2):71-74.
[28]陈绍斌,李国成.消溃灵对乙酸性胃溃疡大鼠一氧化氮和内皮素的影响[J].中国中西医结合脾胃杂志,2001,9(2):76-79.
[29]李长军,王革革,高万良,等.复方消溃灵对消化性溃疡及萎缩性胃炎 患者EGF与EGFR的影响[J].武警医学,2001,12(11):643-645.
[30]樊群,贾春蓉,樊拖迎,等.胃康冲剂防治大鼠胃溃疡的作用[J].中国中西医结合消化杂志,2001,9(4):223-225.
[31]Menowada G,Welch WJ.Clinical implications of the stress response[J].J Clin Invest,1995,95(1):3-12.
[32]李国成,陈训武.健脾益气方对急性胃粘膜损伤大鼠热休克蛋白的影响[J].中国中西医结合杂志,2006,18(3):162-164.
[2]王苑本.消化性溃疡研究现状[J].新消化病杂志,1996,4(3):223.
[3]房殿春,彭志红.胃粘膜屏障功能研究概况(综述)[J].现代消化介入及治疗,2007,12(1):48-52.
[4]王崇文.消化性溃疡的抗幽门螺杆菌与抑酸维持治疗(述评)[J].中华消化杂志,2002,22(2):69-71.
[5]戴高中.论中医药治疗消化性溃疡的地位及优势[J].中国中西医结合消化杂志,2007,15(1):60-61.
[6]李艳,杨拯,王丽梅,等.消化性溃疡动物模型的研究进展[J].西南军医,2007,9(5):83-86.
[7]OkbaeS,AmagaseK.An ovevriew of acetic acidulcer models-the history and State of the art PePtic ulcer research[J].Biol Pharm Bull.2005,28(8):1321-1341.
[8]叶震世,任建林.胃粘液屏障与胃粘膜保护的研究进展[J].世界华人消化杂志,2005,13(21):2578-2581.
[9]李兆申主编.胃粘膜损伤与保护-基础与临床[M].第1版.上海:科技出版社,2004:69-87.
[10]Wallace JL,Granger DN.The cellular and molecular basis of gastric mucosal defense[J].FASEB J,2006;10(7):731-740.
[11]姒健敏.关注生长因子对胃粘膜的保护作用[J].中华医学杂志,2005,8(5):2744-2745.
[12]高娜.黄芪调节免疫功能的研究[J].长春中医药大学学报,2008,24(6):671.
[13]焦红军.党参的药理作用及其临床应用[J].临床医学.2005,25(4):92-93.
[14]吴丽芹,姜惟,顾武军,等.半夏泻心汤对慢性胃炎合并Hp感染大 鼠胃粘液层磷脂氨基已糖的影响[J].中医药研究,2001,17(1):41.
[15]郭一峰,周文丽,张建鹏,等.海螵蛸多糖对小鼠胃粘膜保护作用的研究[J].第二军医大学学报,2008,29(11):1328-1333.
[16]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,2002,8(5):524.
[17]韩广轩,孙义华,罗晓静.中药白及药理作用及临床应用进展[J].药学实践杂志,2004,22(4):24-26.
[18]于辉,李春香,宫凌寿,等.甘草的药理作用概述[J].现代生物医学进展,2006,6(4):77-80.
[19]Kalia N,Brown N J,Jacob S,et al.Studies on gastric mucosal microcirculation.1.The nature of regional variations indiced by ethanol injury[J].Gut,2000,40(1):31-35.
[20]梅武轩,邓兰琼.柴胡桂枝汤对大鼠胃溃疡愈合质量的影响[J].咸宁医学院学报,2000,14(3):172-175.
[21]张学智,周永芬.加味六君子汤治疗合并出血后的上消化道溃疡[J].陕西中医,2000,29(1):2.
[22]刘建平,胡冬菊,宗全和,等.健脾化瘀中药对大鼠胃溃疡愈合质量的影响[J].中国中西医结合杂志,2004,24(7):635-637.
[23]李松华,连超.胃粘液与胃粘膜保护的研究进展.国外医学消化疾病分册2002,22:1-3.
[24]李春艳,刘丽娜,等.一氧化氮与氧自由基在大鼠急性乙醇性胃粘膜损伤中的作用[J].中国病理生理杂志,2004,20(10):1777.
[25]陈绍斌,李国成.乙酸性胃溃疡大鼠一氧化氮、内皮素及表皮生长因子受体相互关系研究[J].中国中西医结合消化杂志,2002,10(5):259-262.
[26]施华秀,任建林.氧自由基与胃粘膜损伤[J].世界华人消化杂志,2005,13(21):2582-2585.
[27]韦维,林寿宁,黄贵华,等.安胃汤对胃溃疡大鼠溃疡修复及表皮生 长因子的影响[J].湖南中医药大学学报,2008,28(6):38-41.
[28]向华,侯小华.胃粘膜保护机制的研究[J].临床消化病杂志,2004,16(2):79-81.
[29]Kusterer K,Buchheit KH,Schade A,Bruns C,Neuberger C,Engel G,Msadel KH.The somatostatin analogue octreotide protects against ethanol-induced microcirculatory stasis and elevated vascular permeability in rat gastric mucosa[J].Eur J Pharmacol 2004;259(5):265-271.
[30]刘劲松,侯晓华.一氧化氮对胃粘膜保护机制的实验研究[J].华中科技大学学报,2004,33(5):592-593.
[31]Heung Mook Shin,全小林.加味参苓白术散对吲哚美辛所致大鼠胃粘膜损伤的保护作用[J].国外医学.中医中药分册,2000,22(5):279.
[32]许春娣.表皮生长因子在消化性溃疡愈合中的作用[J].国外医学儿科学分册2000,24(3):123-124.
[33]时昭红,张介眉,周慧芳,等.促愈颗粒对胃溃疡实验大鼠胃粘膜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,2007,15(1):25-27.
[34]Konturek L,Takeuchi K,Tarnawski A.Gastric mucosal defense and cytoprotection:bench to bedside[J].Gastroenterology.2008 Jul;135(1):41-60.
[35]Lee H,Hansson HA,Norstrom E,et al.Immunoreactivities for epidermal growth factor(EGF) and for EGF receptors in rats with gastric ulcers.Cell Tissue Res,1991,265(2):211-218.
[36]Tarnawski A,Stachura J,Durbin T,et al.Increased expression of epidermal growth factor receptor diring gastric ulcer healing in rats.Gastroenterology.1992 Feb;102(2):695-698.
[37]李长军,张蕙,王革革,等.消溃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.
[38]Dajani E.Is peptic ulcer a prostaglandin deficiency disease?[J].Hum Pathol,1998,17(2):106-107.
[39]Feldman M.Southwestern internal medicine conference:prostaglandins and gastriculcers:From seminal versicle tomisoprostol (Cytotect).Am J Med Sci,1999,300(7):116-118.
[40]Hinsdale JG,Engel JJ,Wilson DE.Prostaglandin E in peptic ulcer disease.Prostaglandins,2001,6(4):495-497.
[41]石以方,洪向秀,尚炽昌,等.加味黄连汤对大鼠慢性胃粘膜损伤PGE_2的影响及病理组织学改变[J].河南中医,2000,20(5):25.
[42]张秋霞,郭淑杰.四逆陷胸汤合方对实验大鼠慢性萎缩性胃炎血清胃泌素、胃粘膜PGE_2的影响[J].北京中医,2001,20(1):37-39.
[43]方尔笠,许宏俐,薛德彬,等.益气化瘀煎剂抗大鼠胃溃疡作用及其机制的探讨[J].中国中西医结合消化杂志,2001,9(4):208-209.
[44]汪建英,李振甲.6-keto-PGE_2和TXB在胃粘膜适应性细胞保护中的作用[J].生理学报,1986,38(5):451-452.
[45]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,2005,14(1):22-24.
[46]姜少芳.中医药治疗消化性溃疡概况[J].河北中医,2007,29(5):463-464.
[47]李冀.中医药治疗消化性溃疡研究进展[J].中医药学刊,2006,24(2):19-21.
[48]叶松,黄鹤,曹芳,等.中药治疗消化性溃疡实验研究进展[J].湖北中医杂志,2004,26(6):56-57.
[49]杨卫文,黎莉,邓亚杰,等.丹参治疗消化性溃疡的疗效及机制探讨[J].中华消化杂志,2002,22(7):438-439.
[1]张绍先.中西医结合治疗消化性溃疡60例疗效观察[J].云南中医杂志,2005,26(3):9-10.
[2]彭世敏.辨证治疗消化性溃疡79例[J].实用中医药杂志,2005,21(4):206-207.
[3]周仲瑛.中医内科学[M].第七版.北京:中国中医药出版社,2004:196.
[4]吴恒中,吴全明.胃脘痛中医辨证与幽门螺旋菌检测的关系初探[J].辽宁中医杂志,2003,11(5):14-17.
[5]李乾构.健胃愈疡片治疗消化性溃疡791例[J].中国中西医结合消化杂志,2004,12(5):291-293.
[6]田养年.胃肠疾病辨治验案4则[J].江苏中医药,2007,39(6):51-52.
[7]林孔孝,李克强.中西医结合治疗消化性溃疡78例[J].浙江中西医结合杂志,2004,5(12):748-749.
[8]罗关靖.中医辨证治疗消化性溃疡98例临床观察[J].河南中医,2003,23(2):29-30.
[9]于世杰.中医辨证治疗消化性溃疡45例[J].辽宁中医杂志,2003,39(5):382-383.
[10]彭连生,胡锡元,金李田,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):150-153.
[11]夏锦军,黄桂勇.胃溃宁胶囊药理实验研究[J].时珍国医国药,2000,11(1):11-12.
[12]李岩,向丽华.黄连药理作用及临床应用[J].甘肃中医,2004,17(12):5-7.
[13]万清信.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):78-81.
[14]陈芝芸,项柏康,朱林喜,等.100味中药对幽门螺旋杆菌和作用的试验研究[J].时珍国医国药研究,1996,7(1):25-26.
[15]乔雪枫,张淑琴.中西医结合治疗与幽门螺旋杆菌(HP)相关的消化性溃疡24例疗效观察[J].中华实用中西医杂志,2004,4(17):3243.
[16]许艺,叶柏,单兆伟,等.中草药单味与复方对幽门菌抑制作用研究[J].中国中西医结合脾胃杂志,2000,8(5):292-293.
[17]宋希仁,焦丛海.大黄治疗幽门弯曲菌阳性的消化性溃疡临床观察 [J].中医杂志,1991,32(5):25-27.
[18]黄玲,易受乡,刘雨姬,等.中医药对胃粘膜损伤保护作用机理研究进展[J].中国中医药信息杂志,2003,10(12):76-78.
[19]王国中,茹新,丁丽华,等.丹参抗大鼠乙酸胃溃疡和防止复发的效果[J].华人消化杂志,2003,6(1):38-39.
[20]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,2002,8(5):524.
[21]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,2005,14(1):22-24.
[22]王毓明,李明诊.川芎嗪对家兔胃粘膜“血流量”影响的实验研究[J].辽宁中医杂志,2002,26(12):565.
[23]唐梅文,王庆高,武青,等.溃疡疡愈合质量的影响因素与中医药干预的研究进展[J].广西中医药,2004,27(3):7-9.
[24]Kμsterer K,Pihan G,Seabo S.Role of lipid peroxidation in gastric mucosal lesion induced by HCL,NAOH or ischemia[J].Am J Physiol,2004,252(15):811-812.
[25]Atμma C,Engstrand L,Holm L.Extracts of Helicobacter pylori reduce gastric mucosal blood flow through a VacA-and CagA-independent pathway in rats[J].Scand J Gastroenterol,2002,33(12):1256-1258.
[26]Heμng Mook Shin,全小林.加味参苓白术散对吲哚美辛所致大鼠胃粘膜损伤的保护作用[J].国外医学·中医中药分册,2000,22(5):279-281.
[27]李长军,李国成,叶四平,等.消费灵治疗消化性溃疡的临床研究[J].中国中西医结合脾胃杂志,2001,9(2):71-74.
[28]陈绍斌,李国成.消溃灵对乙酸性胃溃疡大鼠一氧化氮和内皮素的影响[J].中国中西医结合脾胃杂志,2001,9(2):76-79.
[29]李长军,王革革,高万良,等.复方消溃灵对消化性溃疡及萎缩性胃炎 患者EGF与EGFR的影响[J].武警医学,2001,12(11):643-645.
[30]樊群,贾春蓉,樊拖迎,等.胃康冲剂防治大鼠胃溃疡的作用[J].中国中西医结合消化杂志,2001,9(4):223-225.
[31]Menowada G,Welch WJ.Clinical implications of the stress response[J].J Clin Invest,1995,95(1):3-12.
[32]李国成,陈训武.健脾益气方对急性胃粘膜损伤大鼠热休克蛋白的影响[J].中国中西医结合杂志,2006,18(3):162-164.