半夏泻心汤有效组分总皂苷对HP胃黏膜炎症修复的影响
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摘要
目的：比较半夏泻心汤及其半夏泻心汤有效组分总皂苷对幽门螺杆菌感染相关性胃炎小鼠胃黏膜的保护作用,通过研究半夏泻心汤及其有效组份总皂苷对幽门螺杆菌感染小鼠胃黏膜形态和血清中EGF、TNF-α含量的影响,探讨半夏泻心汤有效组份总皂苷保护和修复幽门螺杆菌导致的胃黏膜损伤的作用机理,为进一步阐述该方作用的物质基础提供科学依据,为临床防治幽门螺杆菌感染性胃部疾病提供实验基础。
方法：小鼠随机分为空白组和造模组,造模组动物予以幽门螺杆菌菌液灌胃造模。造模成功后,将造模组动物随机分组,药物灌胃治疗。治疗结束后,心脏采血处死动物,取胃,取血清。胃组织包埋、切片、HE染色,观察胃黏膜的形态学改变,血清检测各标本中EGF、TNF-α的含量。
结果：
1.胃黏膜炎性细胞浸润情况,全方组、总皂苷组与模型组比较,差异都有统计学意义(P<0.05)；总皂苷组与全方组比较,差异无统计学意义(P>0.05)。
2.尿素酶试验结果,全方组、总皂苷组与模型组比较,差异都有统计学意义(Bonferroni校正法P<0.0083)；总皂苷组与全方组比较,差异无统计学意义(P=0.9999)。
3.血清EGF含量测定结果,模型组与空白组比较,差异有统计学意义(P<0.05)；全方组与模型组比较,差异有统计学意义(P<0.05)。
4.血清中TNF-α含量测定结果,模型组与空白组比较,差异有统计学意义(P<0.05)；全方组、总皂苷组与模型组比较,差异均有统计学意义(P<0.05)；总皂苷组与全方组比较,差异无统计学意义(P>0.05)。
结论：
1、半夏泻心汤及有效组分总皂苷均能抑杀Hp；改善幽门螺杆菌感染小鼠胃粘膜炎症程度。
2、半夏泻心汤全方能调节幽门螺杆菌感染小鼠血清EGF的分泌,有效组分总皂苷没有促进EGF的分泌作用,但能降低幽门螺杆菌感染小鼠血清中TNF-α的含量,可能是通过抗Hp,调节炎症因子TNF-α来保护Hp感染小鼠的胃黏膜。
Objective:Comparison of Banxiaxiexin Decoction and its effective components of Total Saponins on Helicobacter pylori(Hp)-associated gastritis in mice infected with the protective effects of gastric mucosa, through research Banxiaxiexin Decoction and its effective component of total saponins of Hp Helicobacter infections in mice gastric mucosa morphology and serum EGF, TNF-αcontent to explore the decoction and its components of effective protection and restoration of total saponins of Hp cause gastric mucosal damage in the mechanism for further on the side of the material basis for the role of providing a scientific basis for clinical prevention and treatment of Hp infection in the stomach to provide experimental basis for the disease.
Method:Mice were randomly divided into blank group and the model, animal model to model oral bacterium Hp. Successful models will be randomized animal model, drug treatment administered. After the treatment, the heart blood of animals put to death, take stomach, serum. Embedded gastric tissue, biopsy, HE staining to observe the morphological changes of gastric mucosa, serum samples detected by EGF, TNF-a content.
Result:1.Mucosal infiltration of inflammatory cells, The whole group, with a total Saponins group compared with the model group, the differences are statistically significant (P<0.05); total saponins group with side group, there was no significant difference (P> 0.05).2.Urease test results, the whole group, the total Saponins group compared with the model group, the differences are statistically significant (Bonferroni correction P<0.0083); total saponins group with the whole group, there was no significant difference (P= 0.9999).3.Determination of serum EGF results, model group and blank group, the difference was statistically significant (P<0.05); all-party group compared with the model group, the difference was statistically significant (P<0.05).4.Serum TNF-a assay results, the model group and blank group, the difference was statistically significant (P<0.05); The whole group, with total saponins group compared with the model group, the differences were statistically significant (P<0.05); total saponins group and the whole group, there was no significant difference (P> 0.05).
Conclusion:1.Banxiaxiexin Decoctionand and effective components of total Saponins can kill Hp; Helicobacter pylori infection in mice to improve the degree of gastric inflammation.2.Whole decoction Hp infection in mice in order to regulate the secretion of serum EGF and effective component of total saponins did not promote the secretion of EGF, but Hp infection can reduce the serum TNF-αin the content, probably through anti-Hp, inflammatory cytokines TNF-conditioning to protect the gastric mucosa of Hp infection.
方法：小鼠随机分为空白组和造模组,造模组动物予以幽门螺杆菌菌液灌胃造模。造模成功后,将造模组动物随机分组,药物灌胃治疗。治疗结束后,心脏采血处死动物,取胃,取血清。胃组织包埋、切片、HE染色,观察胃黏膜的形态学改变,血清检测各标本中EGF、TNF-α的含量。
结果：
1.胃黏膜炎性细胞浸润情况,全方组、总皂苷组与模型组比较,差异都有统计学意义(P<0.05)；总皂苷组与全方组比较,差异无统计学意义(P>0.05)。
2.尿素酶试验结果,全方组、总皂苷组与模型组比较,差异都有统计学意义(Bonferroni校正法P<0.0083)；总皂苷组与全方组比较,差异无统计学意义(P=0.9999)。
3.血清EGF含量测定结果,模型组与空白组比较,差异有统计学意义(P<0.05)；全方组与模型组比较,差异有统计学意义(P<0.05)。
4.血清中TNF-α含量测定结果,模型组与空白组比较,差异有统计学意义(P<0.05)；全方组、总皂苷组与模型组比较,差异均有统计学意义(P<0.05)；总皂苷组与全方组比较,差异无统计学意义(P>0.05)。
结论：
1、半夏泻心汤及有效组分总皂苷均能抑杀Hp；改善幽门螺杆菌感染小鼠胃粘膜炎症程度。
2、半夏泻心汤全方能调节幽门螺杆菌感染小鼠血清EGF的分泌,有效组分总皂苷没有促进EGF的分泌作用,但能降低幽门螺杆菌感染小鼠血清中TNF-α的含量,可能是通过抗Hp,调节炎症因子TNF-α来保护Hp感染小鼠的胃黏膜。
Objective:Comparison of Banxiaxiexin Decoction and its effective components of Total Saponins on Helicobacter pylori(Hp)-associated gastritis in mice infected with the protective effects of gastric mucosa, through research Banxiaxiexin Decoction and its effective component of total saponins of Hp Helicobacter infections in mice gastric mucosa morphology and serum EGF, TNF-αcontent to explore the decoction and its components of effective protection and restoration of total saponins of Hp cause gastric mucosal damage in the mechanism for further on the side of the material basis for the role of providing a scientific basis for clinical prevention and treatment of Hp infection in the stomach to provide experimental basis for the disease.
Method:Mice were randomly divided into blank group and the model, animal model to model oral bacterium Hp. Successful models will be randomized animal model, drug treatment administered. After the treatment, the heart blood of animals put to death, take stomach, serum. Embedded gastric tissue, biopsy, HE staining to observe the morphological changes of gastric mucosa, serum samples detected by EGF, TNF-a content.
Result:1.Mucosal infiltration of inflammatory cells, The whole group, with a total Saponins group compared with the model group, the differences are statistically significant (P<0.05); total saponins group with side group, there was no significant difference (P> 0.05).2.Urease test results, the whole group, the total Saponins group compared with the model group, the differences are statistically significant (Bonferroni correction P<0.0083); total saponins group with the whole group, there was no significant difference (P= 0.9999).3.Determination of serum EGF results, model group and blank group, the difference was statistically significant (P<0.05); all-party group compared with the model group, the difference was statistically significant (P<0.05).4.Serum TNF-a assay results, the model group and blank group, the difference was statistically significant (P<0.05); The whole group, with total saponins group compared with the model group, the differences were statistically significant (P<0.05); total saponins group and the whole group, there was no significant difference (P> 0.05).
Conclusion:1.Banxiaxiexin Decoctionand and effective components of total Saponins can kill Hp; Helicobacter pylori infection in mice to improve the degree of gastric inflammation.2.Whole decoction Hp infection in mice in order to regulate the secretion of serum EGF and effective component of total saponins did not promote the secretion of EGF, but Hp infection can reduce the serum TNF-αin the content, probably through anti-Hp, inflammatory cytokines TNF-conditioning to protect the gastric mucosa of Hp infection.
引文
[1]柯雪帆,赵章忠,等.《伤寒论》和《金匮要略》中的药物剂量问题[J].中国中药杂志,1983,8(12)：36-38.
[2]柴可夫.慢性胃炎_疑难病中西医结合诊治丛书[M].北京：科学技术文献出版社.1999：270.
[3]Lee et al Lee SK, Lee YC,et al. Low grade gastric mucosa associated lymphoid Tissue lymphoma:Treatment strategies based on 10 Yearfollow-up [J].Wold J Gastroenterol,2004,10(2):223-226.
[4]贺石林.中医科研设计与统计学[M].湖南：科学技术出版社,2003：48.
[5]SCOTT D R, MARCUS E A, WEEKS D L, et al. Mechanisms of acid resistance due to the urease system of Helicobacter pylori[J]. Gastroenterology,2002,123(1):187—95
[6]MONCRIEF M B, HAUSINGER R P. Characterization of UreG, identification of a UreD-UreF-UreG complex, and evidence suggesting that a nucleotide-binding site in UreG is required for in vivo metallocenter assembly of Klebsiella aerogenes urease[J]. Bacteriol,1997,179(13):4081-4086
[7]PetersoWL.Helicobacter pylori and peptic ulcer disease.N.Engl.[J].Med.1991,324: 1043-1048
[8]CAIL, YUSZ, ZHANG Z F.Holicobacter Pylori Infection and Rsk of Gastric Cancer in Changle County, Fujian Province,China.World [J].Gastroenterol,2000, 6:374-376.
[9]夏玉亭,于中麟.慢性胃炎临床研究进展[M],上海科学技术出版社,2003,129
[10]萧树东,江绍基胃肠病学[M],上海：上海科学技术出版社,2000,358-362
[11]肖丽萍,许春娣,鲍昭方等.儿童和成人的Hp相关性胃炎病理变化的对比研究[J].上海医学,2001；24(2)：105-107.
[12]杨占风,林万隆,王晓燕等.Hp感染与胃炎性病变,不典型增生及胃Ca关系的研究[J].中国实验诊断学,2004；8(4)：373-374
[13]刘树阳,魏玲.幽门螺杆菌感染与三种常见慢性胃炎关系的临床分析[J].实用临床医学,2006；7(6),25-2
[14]吴文才,何清华.997例胃粘膜病变幽门螺杆菌感染分析[J].中国医药指南·医药学刊,2005；1(1)：22-23
[15]郭英.幽门螺杆菌感染与胃炎活动性的相关性研究[J].齐齐哈尔医学院学报,2002；23(2)：147.
[16]江素文,刘丽珍.慢性胃炎演变与幽门螺杆菌感染的关系[J].山东医药,2000；40(8)：63.
[17]金珠,林三仁,沈祖尧等,根除幽门螺杆菌对胃粘膜肠化的影响[J].中华消化杂志,2003；23(3)：161
[18]胡品津,曾志荣,林汉良等.幽门螺杆菌的根除与萎缩性胃炎形成和逆转的 动物实验研究[J].中华消化杂志,2000；20(3)：155-158
[19]任之洁,翟祖康.幽门螺杆菌根除后慢性萎缩性胃炎胃粘膜的改变[J].上海第二军医大学学报,2001；21(5)：435-436.
[20]Tucci A,Biasco GP aparo GT. Effect of eradication of Helicobacter pylori in patient fundic atrophic fastritis.NewEngland Journal of Medcine,1997;336:957-958.
[21]Nardone QStraibano S,Rocco A,etal.Effect of Helicobacter pylori infection and its eradication on cell proliferation, DNA status,and on cogene expression in patients with chronic gastritis[J].Gut,1999 44:789-799.
[22]中华医学会消化病学分会.幽门螺杆菌若千问题的共识意见[J].中华消化杂志,2000；20：117-118
[23]Ladas SD.Predictive factors and prevalence of fouicular gastritis in adults with peptic ulcer and nonulcer dyspepsia. Dig Dis Sic,1999;44:1156-1160.
[24]钟志国,洪杰斐.藿连汤治疗幽门螺杆菌相关性胃炎的临床研究[J].福建中医药,2004,35(2)：12
[25]刘松林,梅国强,赵映前.古典医籍对幽门螺杆菌感染相关病证的认识[J].中医药学刊,2004,22(6)：1029—1031
[26]郭霭春.黄帝内经集注[M].北京：人民卫生出版社,1992.320,604
[27]杨春波,柯晓,李秀娟等.脾胃湿热证的临床研究.福建中医学院学报,1999,9(4)：1
[28]郑嘉岗,卢林耿,段艳霞等.慢性胃炎与微观辨证分型的相关性及临床意义[J].中医杂志,2000：41
[29]杨伟群,李亚林.774例慢性胃炎患者的舌象与胃镜象观察[J].福建中医药,1998,29(5)：6
[30]陈泽民,李道本,翁行善等.慢性萎缩性胃炎胃粘膜相微观辨证施治的体会-附300例临床分析[J].北京中医杂志,1990,(1)：27
[31]柴可夫,慢性萎缩性胃炎胃粘膜相微观辨证施治的体会—附121例临床分析[J].山西中医,1991,7(3)：16
[32]郑芝田, 胃肠病学[M].第二版,人民卫生出版社,1992：259
[33]危北海,刘晋生,罗小石等.宏观辨证与微观辨证结合的研究[J].中西医结合杂志,1991,11(5)：301
[34]夏军权,曹蓓蓓,271例幽门螺旋菌感染性慢性胃病辨证分型[J].南京中医学院学报,1992,8(4)：213
[35]李志淳,中医舌诊与胃粘膜相及幽门螺旋菌关系的临床观察[J].四川中医,1994,4(8)：7
[36]王光德,杨旭东.半夏的药理[J].国外医学·中医中药分册,1985,7(5)：24-25.
[37]刘守义,尤春来.半夏抗溃疡作用机理的实验研究[J].辽宁中医杂志,1992,19(10)：42-45.
[38]张小晋,程远,王玘.幽门螺杆菌感染在非街体抗炎药相关性胃病中作用的临床观察[J].国医药导刊.2005,7(5)：356-357。
[39]朱莉,靳蓉,庞勤辉,等.不同菌株类型幽门螺杆菌感染胃肠粘膜的早期病理组织学改变[J].实用儿科临床杂志.2005,20(4)：336-338.
[40]张万岱等.幽门螺杆菌共识意见[J].中华消化杂志,2004,24(2)：126.
[41]苏根.半夏泻心汤加减治疗胃炎溃疡病疗效观察[J].实用中医内科杂志, 1999,13(2)
[42]陈照云,王欣英.半夏泻心汤治疗消化性溃疡44例[J].长春中医学院学报,2002,3(18)：1
[43]郭玉成,李秀芳.半夏泻心汤治疗消化性溃汤病急性活动期疗效分析[J].吉林中医药,2002,7(22)
[44]Isobe H,Okajima K,Harada N,et al.Activated protein C reduces stress-induced gastric mucosal injury in rats by inhibiting the endothelial cell injury.[J] ThrombHaemost,2004Feb；2(2)：313—20
[45]李国平、邓长生等.TNF-α参与消炎痛诱导大鼠胃黏膜损伤机制的探讨[J].中国病理生理杂志,1999,15(9)：814-816
[46]张伟,吴本俨.TNF-α蛋白和mRNA在大鼠药物性胃黏膜损伤表达的研究[J].军医进修学院学报,2001,22(1)：20-22
[47]杨兰泽,高静等。幽门螺杆菌感染患者IL-8和TNF-a水平的检测[J].上海免疫学杂志,2001,21(5)：313
[1]孙艳艳,王雅杰,康熙雄.蛋白芯片技术检测幽门螺杆菌感染的临床价值[J].中华医院感染学杂志,2006,16(12)：1347-1349.
[2]LEUNK R D, JOHNSON P T, David B C, et al. Cytotoxic activity in broth culture filtrates of campylobacter pylori [J]. Med Microbiol,1988,26(2): 93-99.
[3]TUMMURU M K R,COVER T L, BLASER M J. Cloning and expression of a high molecularmass major antigen of Helicobacter pylori:evidence of linkage to cytotoxin production[J]. Infect Immun,1993,61(5):1799—1809.
[4]HAZELL S L. Campyloridis an d Gastritis:Association with Intercellular Spaces and Adaptation to an Environment of Mucus as Important Factors in Colorization of the Gastric Epithellium[J]. Infect Dis,1996,153(4):658.
[5]SCOTT D R, MARCUS E A, WEEKS D L, et al. Mechanisms of acid resistance due to the urease system of Helicobacter pylori[J]. Gastroenterology,2002, 123(1):187—95.
[6]MONCRIEF M B, HAUSINGER R P. Characterization of UreG, identification of a UreD-UreF-UreG complex, and evidence suggesting that a nucleotide-binding site in UreG is required for in vivo metallocenter assembly of Klebsiella aerogenes urease[J]. Bacteriol,1997,179(13):4081-4086.
[7]HIRAYAMA T. Protein tyrosine phosphatase beta, α receptor for Helicobacter pylori vacA toxin[J]. Keio J Med,2002,51,suppl 2:20-23.
[8]YANG Y, DENG CS, PENG J Z, et al. Effect of Helicobacter pylori on apoptosis and apoptosis related genes in gastric cancer cells [J]. Mol Pathol,2003,56(1): 19-24.
[9]ANTOINE GALMICHE, JOACHEM RASSOW, ANNEDOYE,etal. The N-terminal 34KDa fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome C release[J]. EMBO J,2000.19(23): 6361-6370.
[10]TOMASINI ML, ZANUSSI S, SOZZIM, et al. Heterogeneity of cag genetypes in Helicobacter pylori isolates from human biopsy specimens[J]. J Clin Microlori,2003,41(3):976-980.
[11]曹群奋.幽门螺杆菌的毒力基因、vacA基因亚型与上消化道疾病关系的研究[J].中华医院感染学杂志,2007,17(12)：1491
[12]Houghton J, Korah RM, Condon MR,et al. Apoptosis in Helicobacter pylori—associated gastric and duodenal ulcer disease is mediated via the Fas antigen pathway[J]. Dig Dis Sci,1999,44(3):465-478
[13]Piotrowski J, Piotrowski E, Skrodzka D, et al. Induction of acute gastritis and epithelial apoptosis by Helicobacter pyloric lipopolysaccharide[J]. Scand J Gastroenterol,1997,32(3):203—211.
[14]Isomoto H, Mizuta Y, Miyazaki M, et al. Implication of NF—kap-paB in Helicobacter pylori-associated gastritis[J]. Am J Gastroemerol.2000 Oct; 95(10):2768—76.
[15]Zavros Y, Paterson A, Lambert J, et al. Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection[J]. Dig Dis Sci,2000,45(10): 2058—2064.
[16]武一曼,葛振华,周凡,等.人慢性胃炎粘膜内CD3+细胞,S-100+树突状 细胞和(?)NOS表达的意义[J].中国组织化学与细胞化学杂志,2001,10(4)：421.
[17]Ninomiya T, Mastsui H, Akbar SM, et al. localization and characterization of antigen-presenting dendritic cells in the gastric mucosa of murine and human autoimmune gastritis[J]. Eur J Clin Invest,2000,30(4):350.
[18]历兰娜,孔繁智,李端阳.脾虚大鼠螺杆菌模型的实验研究[J].中国中西医结合杂志、1993,6(3)：156
[19]冯莲君,延文.幽门螺杆菌与胃脘痛中医证型的关系[J].现代中西医结合杂志,2000,9(2)：105—106.
[20]傅晓晴,林乾树,李灿东等.慢性胃炎幽门螺杆菌感染与中医舌象证型关系探讨[J].福建中医学院学报,1995,5(2)：5—7.
[21]张琳,扬莲文,杨素君等.中医证型的关系与慢性萎缩性胃炎发病关系防治研究[J].中国中西医结合杂志,1992,12(9)：521
[22]韩子岩,韩松岩,韩树颖.慢性胃炎中医辨证分型与悉尼内镜胃炎分类及幽门螺杆菌感染相关性研究[J].中医杂志,2001,
[23]张万岱,徐智民.幽门螺杆菌研究的现状与展望[J].中国中西医结合消化杂志,2000,9(6)：374—379
[24]于鹰.从湿热探讨Hp相关性胃炎的病机及用药[J].山东中医杂志,2004,23(11)：649
[25]徐州,周德端,段国勋.中药对幽门螺杆菌抑杀作用的实验研究[J].中医医药学报,1993,8(5)：281
[26]杨晓明,谷源平,刘宇慧等.中草药根除幽门螺杆菌的研究[J].中华医学写作杂志,2002,9(18)：1470
[27]钱绍堂.王宏山,谢君亮等,复方瓦楞子冲剂对幽门螺杆菌敏感性的实验研究[J]实用中西医结合杂志,1993
[28]杜新平.吴杰.薛国华等.胃炎平胶囊治疗幽门螺杆菌相关性胃炎113例临床观察[J].中医杂志。2000.41(4)：228
[29]陈飞松,危北海,姚伟等.康胃颗粒治疗幽门螺杆菌相关性胃病228例临床观察[J].中医杂志.2001,42(10)：228
[30]汪悦,单兆伟.益气清热活血法治疗幽门螺杆菌相关性胃炎53例临床观察[J].中医杂志,2002.43(2)：114
[31]史亚祥.益胃宁治疗幽门螺杆菌相关性胃炎88例[J].河北中医。1992,21(2)89
[32]孙风霞,黄炎.加味温胆汤治疗幽门螺杆菌相关性胃炎152例[J].辽宁中医杂志.1999,26(1)：40
[33]常可敏.中西药综合治疗幽门螺杆菌相关性胃炎106例临床观察[J].实用中西医结合杂志.1998,11(6)：527
[34]谢俊范,库健伟,李文欣.中西医结合治疗幽门螺杆菌相关性胃炎200例疗效观察[J].中国中西医结合脾胃杂志,1995.3(1)：49
[35]房静远.单兆伟.张梅涧等.扶正祛邪法治疗幽门螺杆菌感染性胃病的临床与理论探讨[J].中西医结合杂志,1991,11(3)：150
(36]钟志国,洪杰斐.藿连汤治疗幽门螺杆菌相关性胃炎的临床研究[J].福建中医药,2004,35(2)：12
[37]郑学宝,疏肝健脾法治疗幽门螺杆菌相关性胃炎44例临床观察[J].新中医.1993,31(60)：28
[38]祝捷,李宇航,王庆国.半夏泻心汤对功能性消化不良大鼠胃排空及血浆胃动素的影响[J].中华中医药杂志,2002,20(6)：335
[39]王庆国,李宇航,李丽娜.半夏泻心汤对胃电节律失常大鼠胃壁c-kit基因表达水平的影响[J].中国医药学报,2004,16(3)：143
[40]徐颖,颜贵明.半夏泻心汤对胃动力障碍大鼠VIP和胃电的影响[J].中国中医药科技,2004,11(5)：278
[41]张胜,吴春福,车轶等.半夏泻心汤对小鼠胃排空的影响[J].中药药理与临床,2000,16(1)：15
[42]张胜,吴春福,车轶,等.半夏泻心汤对小鼠小肠推进的影响[J].中药药理与临床,2000,16(2)：1
[43]张胜,史国兵.半夏泻心汤对正常大鼠胃底条运动的影响[J].中国中药杂志,2002,27(11)：866
[44]许景峰,王金萍.半夏泻心汤对大鼠胃溃疡及小肠功能的影响[J].中国药业,2002,11(2)：48
[45]张忠,司银楚,白丽敏.半夏泻心汤及其拆方对应激性胃溃疡大鼠P物质的影响[J].中国医药学报,2003,18(11)：669
[46]张忠,司银楚.半夏泻心汤及其拆方对应激性胃溃疡大鼠胆碱能神经元的影响 [J].中国中医基础医学杂志,2005,11(4)：283
[47]王历,刘春红.半夏泻心汤不同服药方法对乙酸性胃溃疡大鼠疗效影响的实验研究[J].中医药信息,2005,22(6)：54
[48]赵琰,李宇航.半夏泻心汤不同性味拆方对胃溃疡大鼠血清胃泌素的影响[J].上海中医药杂志,2004,38(10)：45
[49]赵琰,王庆国,李宇航.半夏泻心汤的不同性味配伍对慢性胃溃疡大鼠胃液分泌及胃蛋白酶活性的影响[J].浙江中医杂志,2004,4：176
[50]吴丽芹,姜惟,姚欣,等.半夏泻心汤对合并幽门螺杆菌感染大鼠慢性胃炎模型胃黏液层磷脂、氨基己糖的影响[J].中国中医药信息志,2001,8(5)：29
[51]姜惟,顾武军,周春祥.半夏泻心汤对慢性胃炎合并幽门螺杆菌感染大鼠一氧化氮的影响[J].中国医药学报,2003,18(11)：666
[52]姜惟,顾武军,周春祥.半夏泻心汤对慢性胃炎合并幽门螺杆菌感染大鼠!的影响[J].天津中医药,2003,20(5)：27
[53]姜惟,顾武军,周春祥.半夏泻心汤对慢性胃炎合并幽门螺杆菌感染大鼠血清IL-2、IL-4的影响[J].中国中医基础医学杂志,2005,11(10)：750
[54]刘喜平,李沛清,席时燕,李雪萍,梁涛.半夏泻心方配伍与诱导BGC-823细胞凋亡关系的血清药理学研究[J].中医杂志,2006,年2月第47卷第2期
[55]谭达全,邓冰湘,周祖怡.半夏泻心汤对幽门螺杆菌相关性胃炎小鼠血清IL-2、IL-8影响的实验研究[J].新中医,2005,37(7)：92
[2]柴可夫.慢性胃炎_疑难病中西医结合诊治丛书[M].北京：科学技术文献出版社.1999：270.
[3]Lee et al Lee SK, Lee YC,et al. Low grade gastric mucosa associated lymphoid Tissue lymphoma:Treatment strategies based on 10 Yearfollow-up [J].Wold J Gastroenterol,2004,10(2):223-226.
[4]贺石林.中医科研设计与统计学[M].湖南：科学技术出版社,2003：48.
[5]SCOTT D R, MARCUS E A, WEEKS D L, et al. Mechanisms of acid resistance due to the urease system of Helicobacter pylori[J]. Gastroenterology,2002,123(1):187—95
[6]MONCRIEF M B, HAUSINGER R P. Characterization of UreG, identification of a UreD-UreF-UreG complex, and evidence suggesting that a nucleotide-binding site in UreG is required for in vivo metallocenter assembly of Klebsiella aerogenes urease[J]. Bacteriol,1997,179(13):4081-4086
[7]PetersoWL.Helicobacter pylori and peptic ulcer disease.N.Engl.[J].Med.1991,324: 1043-1048
[8]CAIL, YUSZ, ZHANG Z F.Holicobacter Pylori Infection and Rsk of Gastric Cancer in Changle County, Fujian Province,China.World [J].Gastroenterol,2000, 6:374-376.
[9]夏玉亭,于中麟.慢性胃炎临床研究进展[M],上海科学技术出版社,2003,129
[10]萧树东,江绍基胃肠病学[M],上海：上海科学技术出版社,2000,358-362
[11]肖丽萍,许春娣,鲍昭方等.儿童和成人的Hp相关性胃炎病理变化的对比研究[J].上海医学,2001；24(2)：105-107.
[12]杨占风,林万隆,王晓燕等.Hp感染与胃炎性病变,不典型增生及胃Ca关系的研究[J].中国实验诊断学,2004；8(4)：373-374
[13]刘树阳,魏玲.幽门螺杆菌感染与三种常见慢性胃炎关系的临床分析[J].实用临床医学,2006；7(6),25-2
[14]吴文才,何清华.997例胃粘膜病变幽门螺杆菌感染分析[J].中国医药指南·医药学刊,2005；1(1)：22-23
[15]郭英.幽门螺杆菌感染与胃炎活动性的相关性研究[J].齐齐哈尔医学院学报,2002；23(2)：147.
[16]江素文,刘丽珍.慢性胃炎演变与幽门螺杆菌感染的关系[J].山东医药,2000；40(8)：63.
[17]金珠,林三仁,沈祖尧等,根除幽门螺杆菌对胃粘膜肠化的影响[J].中华消化杂志,2003；23(3)：161
[18]胡品津,曾志荣,林汉良等.幽门螺杆菌的根除与萎缩性胃炎形成和逆转的 动物实验研究[J].中华消化杂志,2000；20(3)：155-158
[19]任之洁,翟祖康.幽门螺杆菌根除后慢性萎缩性胃炎胃粘膜的改变[J].上海第二军医大学学报,2001；21(5)：435-436.
[20]Tucci A,Biasco GP aparo GT. Effect of eradication of Helicobacter pylori in patient fundic atrophic fastritis.NewEngland Journal of Medcine,1997;336:957-958.
[21]Nardone QStraibano S,Rocco A,etal.Effect of Helicobacter pylori infection and its eradication on cell proliferation, DNA status,and on cogene expression in patients with chronic gastritis[J].Gut,1999 44:789-799.
[22]中华医学会消化病学分会.幽门螺杆菌若千问题的共识意见[J].中华消化杂志,2000；20：117-118
[23]Ladas SD.Predictive factors and prevalence of fouicular gastritis in adults with peptic ulcer and nonulcer dyspepsia. Dig Dis Sic,1999;44:1156-1160.
[24]钟志国,洪杰斐.藿连汤治疗幽门螺杆菌相关性胃炎的临床研究[J].福建中医药,2004,35(2)：12
[25]刘松林,梅国强,赵映前.古典医籍对幽门螺杆菌感染相关病证的认识[J].中医药学刊,2004,22(6)：1029—1031
[26]郭霭春.黄帝内经集注[M].北京：人民卫生出版社,1992.320,604
[27]杨春波,柯晓,李秀娟等.脾胃湿热证的临床研究.福建中医学院学报,1999,9(4)：1
[28]郑嘉岗,卢林耿,段艳霞等.慢性胃炎与微观辨证分型的相关性及临床意义[J].中医杂志,2000：41
[29]杨伟群,李亚林.774例慢性胃炎患者的舌象与胃镜象观察[J].福建中医药,1998,29(5)：6
[30]陈泽民,李道本,翁行善等.慢性萎缩性胃炎胃粘膜相微观辨证施治的体会-附300例临床分析[J].北京中医杂志,1990,(1)：27
[31]柴可夫,慢性萎缩性胃炎胃粘膜相微观辨证施治的体会—附121例临床分析[J].山西中医,1991,7(3)：16
[32]郑芝田, 胃肠病学[M].第二版,人民卫生出版社,1992：259
[33]危北海,刘晋生,罗小石等.宏观辨证与微观辨证结合的研究[J].中西医结合杂志,1991,11(5)：301
[34]夏军权,曹蓓蓓,271例幽门螺旋菌感染性慢性胃病辨证分型[J].南京中医学院学报,1992,8(4)：213
[35]李志淳,中医舌诊与胃粘膜相及幽门螺旋菌关系的临床观察[J].四川中医,1994,4(8)：7
[36]王光德,杨旭东.半夏的药理[J].国外医学·中医中药分册,1985,7(5)：24-25.
[37]刘守义,尤春来.半夏抗溃疡作用机理的实验研究[J].辽宁中医杂志,1992,19(10)：42-45.
[38]张小晋,程远,王玘.幽门螺杆菌感染在非街体抗炎药相关性胃病中作用的临床观察[J].国医药导刊.2005,7(5)：356-357。
[39]朱莉,靳蓉,庞勤辉,等.不同菌株类型幽门螺杆菌感染胃肠粘膜的早期病理组织学改变[J].实用儿科临床杂志.2005,20(4)：336-338.
[40]张万岱等.幽门螺杆菌共识意见[J].中华消化杂志,2004,24(2)：126.
[41]苏根.半夏泻心汤加减治疗胃炎溃疡病疗效观察[J].实用中医内科杂志, 1999,13(2)
[42]陈照云,王欣英.半夏泻心汤治疗消化性溃疡44例[J].长春中医学院学报,2002,3(18)：1
[43]郭玉成,李秀芳.半夏泻心汤治疗消化性溃汤病急性活动期疗效分析[J].吉林中医药,2002,7(22)
[44]Isobe H,Okajima K,Harada N,et al.Activated protein C reduces stress-induced gastric mucosal injury in rats by inhibiting the endothelial cell injury.[J] ThrombHaemost,2004Feb；2(2)：313—20
[45]李国平、邓长生等.TNF-α参与消炎痛诱导大鼠胃黏膜损伤机制的探讨[J].中国病理生理杂志,1999,15(9)：814-816
[46]张伟,吴本俨.TNF-α蛋白和mRNA在大鼠药物性胃黏膜损伤表达的研究[J].军医进修学院学报,2001,22(1)：20-22
[47]杨兰泽,高静等。幽门螺杆菌感染患者IL-8和TNF-a水平的检测[J].上海免疫学杂志,2001,21(5)：313
[1]孙艳艳,王雅杰,康熙雄.蛋白芯片技术检测幽门螺杆菌感染的临床价值[J].中华医院感染学杂志,2006,16(12)：1347-1349.
[2]LEUNK R D, JOHNSON P T, David B C, et al. Cytotoxic activity in broth culture filtrates of campylobacter pylori [J]. Med Microbiol,1988,26(2): 93-99.
[3]TUMMURU M K R,COVER T L, BLASER M J. Cloning and expression of a high molecularmass major antigen of Helicobacter pylori:evidence of linkage to cytotoxin production[J]. Infect Immun,1993,61(5):1799—1809.
[4]HAZELL S L. Campyloridis an d Gastritis:Association with Intercellular Spaces and Adaptation to an Environment of Mucus as Important Factors in Colorization of the Gastric Epithellium[J]. Infect Dis,1996,153(4):658.
[5]SCOTT D R, MARCUS E A, WEEKS D L, et al. Mechanisms of acid resistance due to the urease system of Helicobacter pylori[J]. Gastroenterology,2002, 123(1):187—95.
[6]MONCRIEF M B, HAUSINGER R P. Characterization of UreG, identification of a UreD-UreF-UreG complex, and evidence suggesting that a nucleotide-binding site in UreG is required for in vivo metallocenter assembly of Klebsiella aerogenes urease[J]. Bacteriol,1997,179(13):4081-4086.
[7]HIRAYAMA T. Protein tyrosine phosphatase beta, α receptor for Helicobacter pylori vacA toxin[J]. Keio J Med,2002,51,suppl 2:20-23.
[8]YANG Y, DENG CS, PENG J Z, et al. Effect of Helicobacter pylori on apoptosis and apoptosis related genes in gastric cancer cells [J]. Mol Pathol,2003,56(1): 19-24.
[9]ANTOINE GALMICHE, JOACHEM RASSOW, ANNEDOYE,etal. The N-terminal 34KDa fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome C release[J]. EMBO J,2000.19(23): 6361-6370.
[10]TOMASINI ML, ZANUSSI S, SOZZIM, et al. Heterogeneity of cag genetypes in Helicobacter pylori isolates from human biopsy specimens[J]. J Clin Microlori,2003,41(3):976-980.
[11]曹群奋.幽门螺杆菌的毒力基因、vacA基因亚型与上消化道疾病关系的研究[J].中华医院感染学杂志,2007,17(12)：1491
[12]Houghton J, Korah RM, Condon MR,et al. Apoptosis in Helicobacter pylori—associated gastric and duodenal ulcer disease is mediated via the Fas antigen pathway[J]. Dig Dis Sci,1999,44(3):465-478
[13]Piotrowski J, Piotrowski E, Skrodzka D, et al. Induction of acute gastritis and epithelial apoptosis by Helicobacter pyloric lipopolysaccharide[J]. Scand J Gastroenterol,1997,32(3):203—211.
[14]Isomoto H, Mizuta Y, Miyazaki M, et al. Implication of NF—kap-paB in Helicobacter pylori-associated gastritis[J]. Am J Gastroemerol.2000 Oct; 95(10):2768—76.
[15]Zavros Y, Paterson A, Lambert J, et al. Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection[J]. Dig Dis Sci,2000,45(10): 2058—2064.
[16]武一曼,葛振华,周凡,等.人慢性胃炎粘膜内CD3+细胞,S-100+树突状 细胞和(?)NOS表达的意义[J].中国组织化学与细胞化学杂志,2001,10(4)：421.
[17]Ninomiya T, Mastsui H, Akbar SM, et al. localization and characterization of antigen-presenting dendritic cells in the gastric mucosa of murine and human autoimmune gastritis[J]. Eur J Clin Invest,2000,30(4):350.
[18]历兰娜,孔繁智,李端阳.脾虚大鼠螺杆菌模型的实验研究[J].中国中西医结合杂志、1993,6(3)：156
[19]冯莲君,延文.幽门螺杆菌与胃脘痛中医证型的关系[J].现代中西医结合杂志,2000,9(2)：105—106.
[20]傅晓晴,林乾树,李灿东等.慢性胃炎幽门螺杆菌感染与中医舌象证型关系探讨[J].福建中医学院学报,1995,5(2)：5—7.
[21]张琳,扬莲文,杨素君等.中医证型的关系与慢性萎缩性胃炎发病关系防治研究[J].中国中西医结合杂志,1992,12(9)：521
[22]韩子岩,韩松岩,韩树颖.慢性胃炎中医辨证分型与悉尼内镜胃炎分类及幽门螺杆菌感染相关性研究[J].中医杂志,2001,
[23]张万岱,徐智民.幽门螺杆菌研究的现状与展望[J].中国中西医结合消化杂志,2000,9(6)：374—379
[24]于鹰.从湿热探讨Hp相关性胃炎的病机及用药[J].山东中医杂志,2004,23(11)：649
[25]徐州,周德端,段国勋.中药对幽门螺杆菌抑杀作用的实验研究[J].中医医药学报,1993,8(5)：281
[26]杨晓明,谷源平,刘宇慧等.中草药根除幽门螺杆菌的研究[J].中华医学写作杂志,2002,9(18)：1470
[27]钱绍堂.王宏山,谢君亮等,复方瓦楞子冲剂对幽门螺杆菌敏感性的实验研究[J]实用中西医结合杂志,1993
[28]杜新平.吴杰.薛国华等.胃炎平胶囊治疗幽门螺杆菌相关性胃炎113例临床观察[J].中医杂志。2000.41(4)：228
[29]陈飞松,危北海,姚伟等.康胃颗粒治疗幽门螺杆菌相关性胃病228例临床观察[J].中医杂志.2001,42(10)：228
[30]汪悦,单兆伟.益气清热活血法治疗幽门螺杆菌相关性胃炎53例临床观察[J].中医杂志,2002.43(2)：114
[31]史亚祥.益胃宁治疗幽门螺杆菌相关性胃炎88例[J].河北中医。1992,21(2)89
[32]孙风霞,黄炎.加味温胆汤治疗幽门螺杆菌相关性胃炎152例[J].辽宁中医杂志.1999,26(1)：40
[33]常可敏.中西药综合治疗幽门螺杆菌相关性胃炎106例临床观察[J].实用中西医结合杂志.1998,11(6)：527
[34]谢俊范,库健伟,李文欣.中西医结合治疗幽门螺杆菌相关性胃炎200例疗效观察[J].中国中西医结合脾胃杂志,1995.3(1)：49
[35]房静远.单兆伟.张梅涧等.扶正祛邪法治疗幽门螺杆菌感染性胃病的临床与理论探讨[J].中西医结合杂志,1991,11(3)：150
(36]钟志国,洪杰斐.藿连汤治疗幽门螺杆菌相关性胃炎的临床研究[J].福建中医药,2004,35(2)：12
[37]郑学宝,疏肝健脾法治疗幽门螺杆菌相关性胃炎44例临床观察[J].新中医.1993,31(60)：28
[38]祝捷,李宇航,王庆国.半夏泻心汤对功能性消化不良大鼠胃排空及血浆胃动素的影响[J].中华中医药杂志,2002,20(6)：335
[39]王庆国,李宇航,李丽娜.半夏泻心汤对胃电节律失常大鼠胃壁c-kit基因表达水平的影响[J].中国医药学报,2004,16(3)：143
[40]徐颖,颜贵明.半夏泻心汤对胃动力障碍大鼠VIP和胃电的影响[J].中国中医药科技,2004,11(5)：278
[41]张胜,吴春福,车轶等.半夏泻心汤对小鼠胃排空的影响[J].中药药理与临床,2000,16(1)：15
[42]张胜,吴春福,车轶,等.半夏泻心汤对小鼠小肠推进的影响[J].中药药理与临床,2000,16(2)：1
[43]张胜,史国兵.半夏泻心汤对正常大鼠胃底条运动的影响[J].中国中药杂志,2002,27(11)：866
[44]许景峰,王金萍.半夏泻心汤对大鼠胃溃疡及小肠功能的影响[J].中国药业,2002,11(2)：48
[45]张忠,司银楚,白丽敏.半夏泻心汤及其拆方对应激性胃溃疡大鼠P物质的影响[J].中国医药学报,2003,18(11)：669
[46]张忠,司银楚.半夏泻心汤及其拆方对应激性胃溃疡大鼠胆碱能神经元的影响 [J].中国中医基础医学杂志,2005,11(4)：283
[47]王历,刘春红.半夏泻心汤不同服药方法对乙酸性胃溃疡大鼠疗效影响的实验研究[J].中医药信息,2005,22(6)：54
[48]赵琰,李宇航.半夏泻心汤不同性味拆方对胃溃疡大鼠血清胃泌素的影响[J].上海中医药杂志,2004,38(10)：45
[49]赵琰,王庆国,李宇航.半夏泻心汤的不同性味配伍对慢性胃溃疡大鼠胃液分泌及胃蛋白酶活性的影响[J].浙江中医杂志,2004,4：176
[50]吴丽芹,姜惟,姚欣,等.半夏泻心汤对合并幽门螺杆菌感染大鼠慢性胃炎模型胃黏液层磷脂、氨基己糖的影响[J].中国中医药信息志,2001,8(5)：29
[51]姜惟,顾武军,周春祥.半夏泻心汤对慢性胃炎合并幽门螺杆菌感染大鼠一氧化氮的影响[J].中国医药学报,2003,18(11)：666
[52]姜惟,顾武军,周春祥.半夏泻心汤对慢性胃炎合并幽门螺杆菌感染大鼠!的影响[J].天津中医药,2003,20(5)：27
[53]姜惟,顾武军,周春祥.半夏泻心汤对慢性胃炎合并幽门螺杆菌感染大鼠血清IL-2、IL-4的影响[J].中国中医基础医学杂志,2005,11(10)：750
[54]刘喜平,李沛清,席时燕,李雪萍,梁涛.半夏泻心方配伍与诱导BGC-823细胞凋亡关系的血清药理学研究[J].中医杂志,2006,年2月第47卷第2期
[55]谭达全,邓冰湘,周祖怡.半夏泻心汤对幽门螺杆菌相关性胃炎小鼠血清IL-2、IL-8影响的实验研究[J].新中医,2005,37(7)：92