降逆护膜汤对反流性食管炎抑酸抗复发的实验及临床研究
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摘要
目的:研究COX-2、PCNA、claudin-1在反流性食管炎大鼠模型食管粘膜的表达,及降逆护膜汤对COX-2、PCNA、claudin-1表达的影响;观察降逆护膜汤联合奥美拉唑治疗反流性食管炎的临床疗效及远期复发率。
     方法:采用“不全幽门结扎+贲门肌切开术”制备反流性食管炎大鼠模型,将80只大鼠分为正常组、模型组、假手术组、阳性对照组(奥美拉唑)、中药小剂量组、中剂量组、大剂量组、中西医结合组(降逆护膜汤+奥美拉畔)。给予相应处理后,取食管组织行HE染色,光镜下观察组织病理学变化,用免疫组化的方法检测COX-2、PCNA、claudin-1的表达。选择60例符合反流性食管炎诊断的患者,随机分为治疗组及对照组。治疗组予降逆护膜汤联合奥美拉唑治疗,对照组予奥美拉唑治疗,8周及疗程结束后6个月进行随访。观察两组治疗后症状改善情况及复发情况。
     结果:实验室研究结果显示:降逆护膜汤能显著改变反流性食管炎大鼠模型食管粘膜的病理变化,降逆护膜汤小剂量组、中剂量组、大剂量组、阳性对照组、中西医结合组的食管组织病理变化明显减轻;降逆护膜汤能显著抑制PCNA及claudin-1的表达;COX-2未见明显表达。
     临床观察结果显示:患者治疗前后症状改善RDQ积分变化,治疗组与对照组比较,治疗8周疗效相当,但治疗组6个月复发率远远低于对照组,组间有统计学差异(P<0.05);治疗8周及疗程结束后6个月随访,治疗组的中医症候疗效结果明显高于对照组(P<0.05);疗程结束后6个月随访,治疗组复发率明显低于对照组(P<0.05)。
     结论:降逆护膜汤联合奥美拉唑可以改善反流性食管炎患者的临床症状,降低复发率,提高患者生活质量;降逆护膜汤具有修复食管破损粘膜,抑制细胞过度增殖,控制食管上皮增生和细胞间隙增宽,防止本病进一步发展,对预防Barrett食管、食管腺癌的发生具有积极的意义。
Objective:To study COX-2and PCNA in and claudin-1expression in esophageal mucosa of reflux esophagitis rat model and Jiangni retaining membrane soup of COX-2, PCNA and claudin-1expression; observed Jiangni care The clinical efficacy and recurrence rate of membrane soup plus omeprazole therapy for reflux esophagitis.
     Methods:Incomplete pyloric ligation cardia muscle incision,"Preparation of reflux esophagitis rat model,80rats were divided into normal group, model group and sham group, the positive control group (omeprazole), traditional Chinese medicinesmall dose group, middle dose group, high dose group, integrative medicine group (Jiangni, retaining membrane soup+omeprazole). To give appropriate treatment, the Organization for Esophageal HE staining histopathological changes observed under light microscope to detect COX-2, PCNA and claudin-1expression using immunohistochemical methods.60cases in line with the diagnosis of reflux esophagitis patients were randomly divided into treatment and control groups. The treatment group to Jiangni retaining membrane soup plus omeprazole treatment, control group I omeprazole treatment, six months after the end of8weeks treatment follow-up. Improvement of symptoms and recurrence after treatment were observed.
     Results:The laboratory findings showed:Jiangni retaining membrane soup can significantly change the pathological changes of the esophageal mucosa of reflux esophagitis rat model, soup, small-dose group of Jiangni retaining membrane, the middle dose group, the high-dose group, the positive control group Integrative Medicine group of esophageal pathological changes significantly reduced; Jiangni retaining membrane soup significantly inhibited the expression of PCNA and of claudin-1; The COX-2was no obvious expression.
     .The clinical observation:symptoms improved RDQ points change before and after treatment, the treatment group compared with the control group,8weeks of treatment efficacy, but six months of the treatment group relapse rate is much lower than the control group, statistical differences between the groups (P<0.05); Chinese medicine symptom efficacy outcomes of treatment for eight weeks and the end of June follow-up, treatment group was significantly higher (P<0.05);observed after8weeks of treatment; the six month follow-up after the end of treatment, the treatment group relapse rate was significantly lower than the control group (P<0.05).
     Conclusion:Conclusion:Jiangni cuticle soup plus omeprazole may improve the clinical symptoms of reflux esophagitis in patients with lower relapse rates, and improve patients' quality of life; Jiangni retaining membrane soup has to repair the esophagus damaged mucosa, inhibition of cell over-proliferation, control esophageal epithelial proliferation and cell gap widened, to prevent the further development of the disease, the prevention of Barrett's esophagus, esophageal adenocarcinoma has a positive meaning.
引文
[1]莫剑忠,袁耀宗,邹多武.消化系功能性和动力障碍性疾病[M].上海:上海科学技术出版社,2005:204.
    [2]中华中医药学会脾胃病分会.胃食管反流病中医诊疗共识意见(2009,深圳)[J].中医杂志,2010,51(9):844-847.
    [3]汀涛,龚均,陈谦,等.大鼠反流模型中COX-2.PCNA.CyclinD(?)的表达[J].西安交通大学学报(医学版),2005,26(3):462.
    [4]王永炎,严世芸.实用中医内科学[M].2版.上海:上海科学技术出版社,2009:266-267.
    [5]余利华,单兆伟教授辨治反流性食管炎经验浅析[J].云南中医学院学报,2009,32(6):40-42,52.
    [6]朱生樑,孙永顺,马淑颖,等.胃食管反流病中医证候的多元分析[J].上海中医药杂志,2006,40(10):28-29.
    [7]闫黎娜.李守朝治疗反流性食管炎经验举隅[J].山西中医,2010,26(9):6-7.
    [8]张霞.调肝泄热和胃方治疗反流性食管炎肝胃郁热证的临床研究[D].北京中医药大学,2001.
    [9]姜良铎,杨晋翔.国医大师董建华医学经验集成[M].北京:中国中医药出版社,2010:71-72.
    [10]翟军鹏,李晓宁,陈誩,等.赵荣莱教授治疗胃食管反流病经验[J].北京中医药,2008,27(1):19-20.
    [11]张萍芳.病证结合确立胃食管反流病中医辨证分型标准的思考[J].中国中西医结合消化杂志,2006,14(3):185-187.
    [12]水正,乐毅,樊舟,等.中医辨证分型治疗胃食管反流病52例的临床研究[J].浙江中西医结合杂志,2003,13(7):433-434.
    [13]陈远国.宣清降浊法治疗胃食管反流病[J].四川中医,2005,23(4):25-26.
    [14]胡嘉锡.甘爱萍.柴胡疏肝散加减治疗反流性食炎60例[J].新中医,2009,41(12):84-85.
    [15]闻浩,潘立群,王晓华等.柴莱方治疗反流性食管炎的临床研究[J].江苏中医药,2010,42(9):15-17.
    [16]汀武生,吴国清.益气清胃汤治疗反流性食管炎65例[J].中医杂志,2011,52(8):697-698.
    [17]黄墩煌,吴耀南.半夏泻心汤加减治疗反流性食管炎60例临床观察[J].中国医药导报,2007,4(33):58-59.
    [18]万麟,董蕊,牛卓娅,等.旋复代赭汤加味治疗反流性食管炎41例临床疗效观察[J].四川中医,2004,22(10):58.
    [19]杨健康.加味小陷胸汤治反流性食竹炎疗效观察[J].辽宁中医药大学学报,2007,9(1):90-91.
    [20]王桂花,赵玉武.黄芪建中汤加减治疗胃食管反流病40例体会[J].甘肃中医,2004,17(7):16-16.
    [21]江超先,刘兴勤.半夏泻心汤配合针剌治疗胃食管反流病的临床观察[J].中国康复,2010,25(2):135-136.DOI:10.3870/zgkf.2010.02.023.
    [22]缪奇祥.穴位注射配合西药治疗肝汁反流性胃炎30例临床研究[J].中医杂志,2002,43(3):182—187.
    [23]周国赢.电针加耳针治疗反流性食管炎84例[J].中国中医药信息杂志,2004,11(10):907—909.
    [24]张瑞明,魏玉静.穴位按摩配合西药治疗反流性食管炎100例[J].中医杂志,2001,42(1):56.[25]马日海.纠正7-10胸椎关节错位治疗反流性食管炎[J].按摩与导引,2005,21(4):16.
    [26]萧树东,许国铭.中华胃肠病学[M].北京:人民卫生出版社,2008:292.
    [27]曾启全,简永英,周波.和降方治疗反流性食管炎的临床观察[J].四川中医,2009,27(10):55-56.
    [28]张华军.雷贝拉唑联合枳术宽中胶囊治疗反流性食管炎疗效观察[J].人民军医,2010,53(10):757-758.
    [29]古村博久.反流性食管炎的复发问题[J].日本医学介绍,2002 23(3):58.
    [30]Sandler RS,Everhart JE,Donowitz M,et al. The burden of 8elected digestive diseages in the United States.Gastroenterology,2002,122:1500-1511.
    [31]潘国宗,许国铭,郭慧平等.北京上海胃食管反流症状的流行病学调查[J].中华消化杂志,1999,19(4):223.
    [32]Haggitt RC. Histopathology of reflux-induced esophageal and supraesophageal injuries. Am J Med,2000,108:109.
    [33]林文博.返流性食管炎600例内镜诊断分析[J].医学信息,2006,19(5):904-905.
    [34]王进海,罗金燕,龚均,等.反流性食管炎的流行病学及临床研究[J].中华消化内镜杂志,2000,17(6):345-348.
    [35]Kahrllas P J,Smoking and gastroesophageal reflux disease[J].Dig Dis,1992,10(2):61-64.
    [36]孙晓红,柯美云,王志凤,等.膈脚屏障作用及食管体部的清除功能在食管反流中的作用.中国医学科学院学报,2002,24(3):289-293.
    [37].Mei yun Ke,Xiao hong Sun,Zhi feng Wang. Effect of three test-meal on transient lower esophageal sphincter relaxation(TLESR) in healthy subjects and mechanism of gastroesophageal reflux.Gastroenterology,2002,122:A580.
    [38]杨晓梅,沈皓,马世华,等.内镜检查中反流性食管炎及相关因素的调查分析[J].中国内镜杂志,2005,11(3):265-266,273.
    [39]李巍,贾芳,张澎田,等.反流性食管炎1405例临床和内镜特点分析[J].中国实用内科杂志,2008,28(9):738-741.
    [40]王雯,许国铭,李兆中,等.胃及十二指肠液对食管粘膜损伤的实验研究[J].中华消化杂志,2000,20(4):240-242.
    [41]Waston RGP,Tham TCK,Johnston BJ,et al.Double blind cross-over placebo controlled study of omeprazoie in the treatment of patients with reflux symptoms and physiological levels of acid reflux the "sensitive oesophagus",Gut,1997,40:587-590.
    [42]Li YM;Du J;Zhang H epidemiological investigation in outpatients with symptomatic gastroesophageal reflux from the department of medicine in zhejiang province,east China [J]. J gastoenterol Hepatol,2008,23(2):283-289.
    [43]Baker LH;Lieberman D;Oehlke M.Psychological distress in patients with gastroesophageal reflux disease [J].Am J Gastroenterol,2008,90(10):1797-1083.
    [44]Johnston BT;Lewis SA;Love AHG Do heartburn sufferers have a specific personality profile?[J].Gastroenterology,1992,102(suppl Ⅱ):A91.
    [45]李益农,杨雪松.消化系统疾病药物治疗学[M].北京:清华大学出版社,2008:32.
    [46]向明确,谢文义,袁晓英,等Barrett食管组织中COX-2和Bcl-2的表达与癌变风险[J].第四军医大学学报, 2008,29(19):1807-1810.
    [47]袁耀宗,邹多武,汤玉著,等.胃食管反流病的蒙特利尔(Montreal)定义和分类—基于循证医学的全球共识[J].中华消化杂志,2006,26(10):686-689.
    [48]中华内科杂志编辑委员会.胃食管反流病高峰论坛会议纪要(2011,深圳)[J].中华内科杂志,2011,50(8):698-700.
    [49]中国胃食管反流病研究协作组.反流性疾病问卷在胃食管反流病诊断中的价值[J].中华消化杂志,2003,23:651-654.
    [50]VakilN, van Zanten SV,KahrilasP, et a.l TheMontreal definition and classification of gastroesophageal reflux disease:a global evidence-based consensus[J]. Am J Gastroentero,l 2006,101 (8):1900-1920.
    [51]向雪莲,许军莫,侯晓华.消化内科门诊胃食管反流病诊断问卷诊断胃食管反流病的状况及症状特征分析[J].临床内科杂志,2010,27(3):185-187.
    [52]Lagorce C, ParafF,Vidaud D,etal.Cyclooxygenase-2 is expressed frequently and early in Barrett's oesophagus and associated adeno-carcinoma[J].Histopathology,2003,42(5):457-465.
    [53]Koga Y, Kunano H, Sugimachi K. Biologic characteristics of esophageal epithelial dysplasia assessed by proliferating cell nuclear antigen. Cancer,1996,77:237.
    [54]王天佑,刘宾,王立东等.增殖细胞核抗原和p53在反流性食管炎黏膜的表达及其意义[J].中华内科杂志,2002,41(1):3942.
    [55]叶萍,李兆中,许国铭等.反流性食管炎和食管腺癌组织中P16、P53、PCNA表达及其临床意义[J].解放军医学杂志,2000,25(5):326.
    [56]李春婷,沈水杰,杜斌等.健脾疏肝方对反流性食管炎大鼠模型食管组织病理及PCNA的影响[J].世界华人消化杂志,2007,15(7):733-736.
    [57]Langbein L,Grund C,Tight junctions and compositionally related junctional structures in Mammalian stratified epithelia and cell cultures derived therefrom.Eur J Cell Biol.2002 Aug;81(8):419-35
    [58]AsaokaD,Miwa H,Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis.J Gastroenterol.2005 Aug:40(8):781-90.
    [59]Miwa H,AsaokaD,GERD and tight junetion proteins of the esophageal mueosa.Nippon Rinsho.2004Aug;62(8):1441-6.
    [60]王雯,李兆申,许国铭,等.不同方式建成3种反流性食管炎模型[J].解放军医学志,2000,25(3):171-173.
    [61]中华医学会消化内镜学分会.反流性食管炎诊断及治疗指南(2003年)[J].中华消化内镜杂志,2004,21(4):221-222.
    [62]中华中医药学会脾胃病分会.胃食管反流病中医诊疗共识意见(2009,深圳)[J].中医杂志,2010,51(9):844-847.
    [63]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002:124-151.
    [64]兰进,杨世林,郑玉权等.黄连的研究进展[J].中草药,2001,32(12):1139-1141.
    [65]秦彩玲,刘君英,程志铭.黄连汤对实验性胃粘膜损伤团.中国中药杂志,1994,19(7):427-428.
    [66]张明发,沈雅琴,许青媛等.吴茱英温中止痛药理研究[J].中药材,1991,14(3):39.
    [67]陈蔚文,蓝韶清,李茹柳.等.左金丸抗溃疡及抑制胃液分泌的实验研究[J]广州中医学院学报,1991,8(2-3):224-226.
    [68]代二庆,李海英,赵占考等.旋覆代赭汤及其拆方对大鼠离体食管肌条收缩活动的影响[J].现代中西医结合杂志,2004,13(10):1268-1270.
    [69]于强,袁红霞,崔乃强等.旋覆代赭汤对酸性反流性食管炎模型大鼠血浆胃动素水平的影响[J].中医药学刊,2003,21(6):890-891.
    [70]Kimara Y;Yokoi K;Matsushita N;Okuda H Effects of flavonoids i slat ed from Scutellariae radix on the production of tissue-type plasminogen activat or and plasminogen activator inhibitor-1 induced by thrombin and thrombin rece ptor agonist peptide in cultured human umbilical ven endothlial cell 1997(08).
    [71]李贵海.枳壳挥发油含量对小鼠胃肠推进的影响闭.中药饮片,1993,21(1):20.
    [72].魏江洲,徐红丽,李扬等.海螵峭多糖的分离纯化及生物学活性研究[C].国家“863”计划资源环境技术领域第三届海洋生物高技术论坛论文集.2005:325-330.
    [73]孙仁山,陈晓红,程天民,等.白芨对大鼠创面愈合几个要素的影响[J].中国临床康复,2003,7(29):3927-3929.

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