愈肠汤对溃疡性结肠炎大鼠影响的实验研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
溃疡性结肠炎(Ulcerative Colitis UC简称溃结)是一种病因未明的结肠粘膜炎症。多为慢性过程,患者病情轻重不一,以腹泻、脓血或粘液便、腹痛、里急后重为主要症状。病程迁延,症状反复,被世界卫生组织列为现代难治性疾病之一。本病在欧美国家十分常见,我国通过多中心回顾性调查近14年溃结病例,显示我国溃结发病正呈逐年上升趋势。目前溃结病因尚不十分明确,现代医学认为遗传、感染、免疫、心理及环境因素与溃结发病有一定关系,氨基水杨酸类、皮质激素、免疫抑制剂等为主要治疗药物,但存在明显副作用。
     中医多认为溃结发病主要为外感六淫、饮食不节、情志失调、劳倦内伤等因素。脾虚是发病之根本,多种致病因素导致脾失健运,湿热蕴结肠腑,大肠传导失司,肠络受损,血败肉腐,最终内溃成疡。采用内服、灌肠、内外合治、针灸等方法治疗溃结取得了一定疗效。因此深入探寻溃结中医病因病机及证治规律,已成为提高溃结临床疗效与抗复发的关键问题。本文基于中医理论、现代研究及临床实践经验提出“肺脾功能失调、痰瘀阻络”为溃结主要病机之一,认为肺脾功能失调为发病之本、痰瘀阻络为致病之标,提出“宣肺健脾、化痰行瘀”之法,宣肺则肺宣发肃降功能恢复正常、健脾则脾复健运,使水液得以输布,血行得以通畅,又肺功能正常,将促大肠传导功能恢复正常。同时因痰浊、瘀血粘滞难去,在宣肺健脾治本之时,应用化痰行瘀以治标,肺脾强、痰瘀祛则达到治疗溃结的目的。同时深入、系统进行了愈肠汤干预溃结的实验研究,希望借此对中医药防治难治性疾病进行有益的探索。
     本实验研究分五个部分,从组织形态学、生物化学、免疫组织化学、分子生物学不同层次探讨“肺脾功能失调,痰瘀阻络”病机要素,从细胞因子、结肠上皮细胞凋亡、血液流变学等多个靶点研究“宣肺健脾、化痰行瘀”中药愈肠汤治疗溃结的作用机制。
     1愈肠汤对溃疡性结肠炎大鼠结肠组织形态学影响
     通过对溃结大鼠结肠组织形态学观察,探讨“宣肺健脾、化痰行瘀”中药愈肠汤对溃结大鼠结肠组织形态学影响。结果显示溃结模型组结肠黏膜充血、水肿、弥漫性多发糜烂或溃疡,镜下黏膜固有膜内有弥漫性、慢性炎症细胞及中性粒细胞浸润,隐窝有急性炎症细胞浸润等。愈肠汤组溃结大鼠结肠黏膜轻度充血水肿,未见糜烂、溃疡,镜下黏膜无溃疡,黏膜固有层内有少量淋巴细胞、浆细胞、嗜酸粒细胞浸润,结肠黏膜损伤大体观及结肠黏膜病理积分与模型组比较有统计学意义。说明“宣肺健脾、化痰行瘀”中药愈肠汤能减轻结肠组织组织损伤,促进溃结结肠病变组织修复,治疗溃结有效。
     2愈肠汤对溃疡性结肠炎大鼠氧自由基的影响
     通过对溃结大鼠MDA含量、SOD活性的研究,探讨痰与溃结发病的关系,及“宣肺健脾、化痰行瘀”中药愈肠汤治疗溃结的作用机制。结果显示愈肠汤组与模型组比较MDA含量降低,SOD活性增高,且有统计学意义。说明“宣肺健脾,化痰行瘀”中药愈肠汤具有祛除痰邪,降低MDA含量,增高SOD活性,清除氧自由基,抑制脂质过氧化反应,降低结肠组织黏膜损伤作用。提示溃结大鼠可能存在“痰”的病机要素,祛除痰邪,降低MDA含量,增高SOD活性,清除氧自由基,抑制脂质过氧化反应,降低结肠组织黏膜损伤是中药愈肠汤治疗溃结的可能作用机制之一。
     3愈肠汤对溃疡性结肠炎大鼠血液流变学的影响
     通过对溃结大鼠全血粘度、血浆粘度、全血还原黏度、红细胞压积的研究,探讨血瘀与溃结发病的关系及“宣肺健脾、化痰行瘀”中药愈肠汤治疗溃结的作用机制。结果显示愈肠汤组与模型组比较全血粘度、血浆粘度、全血还原黏度、红细胞压积降低,且有统计学意义。说明“宣肺健脾、化痰行瘀”中药愈肠汤通过活血化瘀,祛除瘀邪,改善高凝状态,改善结肠组织乏氧及微循环障碍。提示溃结大鼠可能存在“瘀”的病机要素,活血化瘀,祛除瘀邪,改善高凝状态,改善结肠组织乏氧及微循环障碍是中药愈肠汤治疗溃结的可能作用机制之一。
     4愈肠汤对溃疡性结肠炎大鼠结肠黏膜上皮细胞凋亡及其调控基因Bcl-2、Bax蛋白表达的影响
     通过对溃结大鼠结肠黏膜上皮细胞凋亡及凋亡调控基因表达的研究,探讨脾虚与溃结大鼠结肠黏膜屏障功能的关系,以及“宣肺健脾、化痰行瘀”中药愈肠汤治疗溃结的作用机制。结果显示愈肠汤组与模型组比较溃结大鼠结肠黏膜上皮细胞凋亡减慢,Bcl-2蛋白表达升高,Bax蛋白表达降低。说明“宣肺健脾、化痰行瘀”中药愈肠汤具有健脾,扶助人体正气,提高凋亡调控基因Bcl-2表达,降低Bax表达,减慢结肠黏膜上皮细胞凋亡速率,保护结肠黏膜屏障功能的作用;提示脾虚可能与溃结发病密切相关,健脾,扶助人体正气,提高凋亡调控基因Bcl-2表达,降低Bax表达,减慢结肠黏膜上皮细胞凋亡速率,保护结肠黏膜屏障功能是“宣肺健脾、化痰行瘀”中药愈肠汤治疗溃结可能作用机制之一。
     5愈肠汤对溃疡性结肠炎大鼠结肠组织TNF-α蛋白及mRNA表达的影响
     通过对溃结大鼠结肠组织TNF-α蛋白及mRNA表达的研究,探讨脾虚、肺气不利与溃结发病的关系及“宣肺健脾、化痰行瘀”中药愈肠汤治疗溃结的作用机制。结果显示愈肠汤组与模型组比较溃结大鼠结肠组织TNF-α蛋白及TNF-αmRNA表达下降。说明“宣肺健脾、化痰行瘀”中药愈肠汤具有宣肺健脾,提高机体防御能力,降低促炎因子TNF-α蛋白及mRNA表达,调节机体免疫功能,减轻结肠黏膜损害作用。提示脾虚、肺气不利与溃结发病密切相关。宣肺健脾,提高机体防御能力,降低促炎因子TNF-α蛋白及mRNA表达,调节机体免疫功能,减轻结肠黏膜损害是“宣肺健脾、化痰行瘀”中药愈肠汤治疗溃结的可能作用机制之一。
The Research of experience on the influence of "YU CHANG TANG" toUlcerative Colitis Mouse
     Specialty: internal medicine of TCM Graduate student: Wang xiliGuiding teacher: Professor Shi yan
     Ulcerative Colitis (UC) is one kind of inflammation of unknownreason of colitis. The course is mostly chronic .Some patients areserve, and some patients are not. The main symptoms are diarrhea,stool of pus and blood or sticky fluid, pain of abdomen and tenesmus,it is called one of diseases that are difficult to cure by WHO.Itis common in Europe and America, and incidence of disease isincreasing these years in our country. Now the reason of the diseaseis not very clear. Modern medicine think that there is somerelationships between heredity, infection, immunity, psychology andthe reason of the disease. The main treating medicines areaminosalicylic acid, corticotropin and immunosuppressivepreparation and so on , but the side-effect are obvious.
     TCM think that the reasons of UC mainly are six-excess externalcontraction, dietary irregularities, disfunction of affect-mind,and taxation fatigue internal injury, etc. The main reason isspleen vacuity. Many reasons cause spleen failing to move andtransform, damp-heat brewing in the intestines, large intestinesfailing to conveyance, the network vessels of intestines, rottenblood and meat, at last being ulceration. The ways by taken orally,enema, internal and external treating and acupuncture treating UChave achieved curative effect. So the key question on improving theclinic curative effect and resisting recurrence is finding out the reason, pathomechanism and rules of patterns and treating of TCMof UC. The essay put forward that disfunction of the lung and spleen,phlegm-stasis obstructing the network vessels is one ofpathomechanisms based on the theory of TCM, modern research andclinic experience. It thinks that disfunction of the lung and spleenis the root of the disease, and phlegm-stasis obstructing the networkvessels is the tip. Through the theory it put forward the method ofdiffusing the lung and fortifying the spleen, transforming phlegmand moving stasis. Diffusing the lung make it recover the functionof promoting diffusion and depurativing downbearing, andfortifying the spleen make it recover fortifying and transforming.So the liquid can transporting and the blood can unobstruct with thenormal function of lung promote the large intestine recover thefunction of conveyance. Because phlegm and stasis are sticky, asdiffusing the lung and fortifying the spleen treat the root,transforming phlegm and moving stasis treat the tip. The aid oftreating UC is strengthening the spleen and lung, dispelling thephlegm-stasis. At the same time researching the theory ofpathomechanism of UC and the systematic experiments that testify thetheory is established. Hoping that will be good to probe how totreating diseases difficult to cure by TCM.
     The experience is divided into five parts. Fromimmunohistochemistry, tissue morphology, biological chemistry andmolecular biology etc we discuss the reason of disfunction of thelung and spleen, phlegm-stasis obstructing the network vessels. Fromthe cells, hemorheology, apoptosis of epithelial cells of intestineetc we discuss the mechanism of Yuchang tang.
     1 the influence of Yuchang tang to tissue morphology of intestineof UC mouse
     We discuss the influence of Yuchang tang to tissue morphology ofintestine of UC mouse by observing it. UC model group showedintestinal membrane edema, ulcer, corrupt and the invasion ofinflammation cells and leukocytes. Yuchang tang group showedintestinal membrane little edema, do not ulcer and corrupt. Thereare some invasions of lymphatic cells, plasmacells and EOS. It showedthat Yuchang tang is good to UC.
     2 the influence of Yuchang tang to oxygen radicals of intestineof UC mouse
     We discuss the relationships between phlegm and UC, and themechanism of Yuchang tang to UC by studying MDA, the activity of SODof UC mouse. The result is that MDA of Yuchang tang group is morethan model group, and the activity of SOD is stronger It shows thatYuchang tang can do away with phlegm evil and oxygen radicals, andprotect the membrane of intestine. The mechanism maybe is that phlegmis the reason of the disease, and the good way of Yuchang tang toUC is doing away with phlegm evil and oxygen radicals.
     3 the influence of Yuchang tang to hemorheology of intestine ofUC mouse
     We discuss the relationship of stasis between UC and the mechanismof Yuchang tang to UC by studying the blood. It shows that Yuchangtang can quicken the blood and transform stasis, lessen the harm oftissue ofintestine. It shows that stasismaybe is the reason of UC,and the mechanism of Yuchang tang to UC is quickening the blood andtransforming stasis.
     4 the influence of Yuchang tang to apoptosis of epithelial cellsof intestine of UC mouse
     We discuss the relationship between spleen vacunity and theprotection of membrane of mouse intestine by studying apoptosis of epithelial cells of intestine of UC mouse. The epithelial cells ofintestine of UC mouse of model group is quicken, the expression ofprotein Bcl-2 is lessen, the expression of protein Bax is higher.It shows that spleen vacunity maybe is the reason of UC, and themechanism of Yuchang tang to UC is supplementing spleenqi, raisingright qi, lesseningapoptosis of epithelial cells of intestine andprotecting the membrane of intestine.
     5 the influence of Yuchang tang to expression of TNF-αproteinand mRNA of intestinal tissue of UC mouse
     We discussed the relationship between vacunity of spleen,inhibition of lung qi and the reason of UC and the mechanism ofYuchang tang to UC through the research of expression of TNF-αprotein and mRNA of intestinal tissue of UC mouse. The result shownthat the expression of protein TNF-αand TNF-αmRNA promoted ingroup of model, and that dropped in group of Yuchang tang. It shownthat Yuchang tang can recover the function of the lung and spleen,regulate the immunity and protect the membrane of intestine. It shownthat there is close relationship between vacunity of spleen,inhibition of lung qi and the reason of UC. The mechanism of Yuchangtang to UC maybe is recovering right qi, reducing the expression ofinflammation factor and reducing the harm of intestinal membrane.
引文
[1] 中国炎症性肠病协作组,3100例溃疡性结肠炎住院病例回顾分析,中华消化杂志,2006年26(6):368—372。
    [2] 秦成勇.炎症性肠病的药物治疗.山东卫生.2005:5:53-54
    [3] 中华医学会消化病学分会,对炎症性肠病诊断治疗规范的建议(2000年),现代实用医学,2003,15(10):656—659。
    [4] 郑礼,等.大鼠溃疡性结肠炎模型的实验研究.中国药理学通报.1998;14(4):370—2.
    [5] 朱峰,等.细胞免疫性实验性结肠炎动物模型的建立和髓过氧化物酶及超氧化物歧化酶的检测[J],中国医学科学院学报,1997;20:271。
    [6] Tjandra K, et al. Experimental colitis attenuates development of toxin-induced cholangitis in rats[J].Dig Dis Sci, 2002,47:1216.
    [7] Mizoguchi Emiko, Mizoguchi Atsushi,Takedatsu Hidetoshi, etal. Role of tumor necrosis factor receptor 2(TNFR_2)in colonic epithelial hyperplasia and chronic intestinal inflammation in mice[J].Gastroenterology, 2002,122(1):134-144
    [8] Muller S, Lory L, Corazza N C, et al. Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease. Am J Pathol, 1998, 152: 261-268.
    [9] 卢艺涛,等.溃疡性结肠炎患者相关细胞因子的试验性研究。现代预防医学,2005,32(7):735—736
    [10] 王雪茜,王新月,杨莉莉.不同给药途径对大鼠溃疡性结肠炎结肠黏膜EGF表达的影响.世界华人消化杂志.2006;14(29):2872—2875
    [11] 秦成勇.炎症性肠病的药物治疗.山东卫生.2005;5:53-54
    [12] 张正利,蔡淦.溃疡性结肠炎中医治疗及理论探讨.陕西中医,2001,22(7):405~406
    [13] 段荣章.慢性溃疡性结肠炎从肝论治.河南中医.1996;16(6):342
    [14] 张理,黄发盛.宏观与微观结合论治溃疡性结肠炎血瘀证.光明中医.2004;19(4):21—23
    [15] 焦君良,要丽瑛,李士军,刘桂缺.从痈论治溃疡性结肠炎初探.中国中西医结合脾胃杂志.2000:8(2):100—101
    [16] 沈洪,朱萱萱,刘万里等.调理脾肺法对实验性大鼠溃疡性结肠炎作用机理的研究.江苏中医药.2002:23(12):53—54
    [17] 俞娜珍.从瘀论治慢性非特异性结肠炎.中医药学报.2002;30(3):45—46
    [18] 吕永惠,钟东江.溃疡性结肠炎患者血液流变学与中医辨证关系.世界华人消化杂志.2001;9(8):977—978
    [19] 张永艳.宣肺健脾汤治疗慢性溃疡性结肠炎68例.河北中医,2000,22(8):599—600
    [20] 孔莹,柯启贤.自拟健脾清肠汤治疗慢性溃疡性结肠炎的疗效观察.辽宁中医学院学报.2004;6(3):191
    [21] 卞耀臣,李振武.温里化痰法治疗慢性溃疡性结肠炎60例.山东中医杂志.2004;23(8):472
    [22] 劳国平.中医辨证加化痰药治疗慢性非特异性溃疡性结肠炎的疗效观察.广西医科大学学报.2000;17(5):889—890
    [23] 连建学,刘宏平,刘卫华.活血化瘀中药治疗溃疡性结肠炎62例.陕西中医.2006;17(1):47-49
    [24] 曾庆祥;衷诚伟.异功散及其加味方对小儿脾虚证患者临床疗效及免疫功能的影响[J].中医杂志.2003;44(3)197—198。
    [25] 修宗昌;等.脾虚免疫学机制[J].中国中医药信息杂志.2003;10(4):10—13。
    [26] 徐世杰,等.实验性脾虚痹证的黏膜免疫学机制研究.2003;9(12):35—38。
    [27] 匡调元.中医病理研究.上海科学技术出版社.1980:145。
    [28] 靳文学,杨宇.从黏膜免疫系统看“肺与大肠相表里”.四川中医.2005;23(12):1—3。
    [29] 刘维庆.免疫与中医正气关系探微.陕西中医.2003:24(7):629—632。
    [30] 李泽庚,等.肺气虚证模型大鼠血清ICAM-1、IL-8的水平变化.光明中医.2005;20(6):38—40。
    [31] 李泽庚,等.肺气虚证患者NK细胞活性、TNF和IL-2的变化及临床意义.中国中医急症.2005;14(4):334—336。
    [32] 占宏伟,等.肠易激综合征不同中医证型前列腺E_2和环核苷酸的变化及意义.[J]浙江中医 学院学报.2000;24(3):16—19。
    [33] 周吕.胃肠生理学.北京科技技术出版社.1991:726—727。
    [34] 廖荣鑫.痰病的现代研究及思路探讨.贵阳中医学院学报.2001;23(4):1—2.
    [35] 李保东,等.中风痰证与SOD及MDA关系的探讨[J].辽宁中医杂志,1997;24(9):389.
    [36] 滕修胜.痰概念的演变及内涵[J].中国中医基础医学杂志,1997;3(3):49.
    [37] 方永奇,等.心血管痰证患者血液流变学及植物神经的变化[J].中西医结合杂志。1989;(9):536.
    [38] 王少华,等.丹参对大鼠溃疡性结肠炎SOD活性和MDA含量影响的实验研究[J].中国肛肠病杂志.2000;20(7):3.
    [39] 黄俊,等.大鼠实验性溃疡性结肠炎中N0、MDA、SOD的变化.武汉大学学报(医学版).2002;23(2):146—148.
    [40] 周燕红,刘毅飞.姜黄素对溃疡性结肠炎脂质过氧化损伤大鼠的保护作用.成宁学院学报(医学版).2005;19(4):280—282.
    [41] 徐德亮,穆平等.溃疡性结肠炎血液流变学及抗凝的临床研究,胃肠病学和肝病杂志,2005,14(4):413—415。
    [42] 吕永慧,钟东江.溃疡性结肠炎患者血液流变学与中医辨证关系.世界华人消化杂志,2001;9(8):977—978.
    [43] 王琦、叶家农.肥胖人痰湿体质的血液流变学及甲皱微循环研究[J].中国中医基础医学杂志,1995,1(1):52
    [44] 陈银玲.从现代研究论“痰瘀同源”.内蒙古中医药,1994,2:33-34
    [45] 邵启祥,等.黄芪对小鼠免疫功能的调节作用[J].中国实验临床免疫学杂志,1996;8(1):48
    [46] 许爱霞,等.党参多糖抗衰老作用机制的实验研究.中国现代应用药学杂志,2006;23(8):729-731
    [47] 郑虎占等.中药现代研究与应用.第1卷.学苑出版社,3729
    [48] 吕青源等.白术抗衰老作用研究.现代应用药学,1996;13(5):26
    [49] Ji Young Lee, Jae Wook Yoon, Cheong Tae Kim, et al. Antioxidant activity of phenylpropanoid esters isolated and identified Platycodon gmndiflorum A. DC.[J]. Phytochem istry, 2004; 65: 3033
    [50] 宋志军等.山珍王口服液对大鼠免疫功能的影响,广西医科大学学报,1995:12(1):52-54
    [51] 范伟忠等.薏苡仁油对小鼠移植性肿瘤的影响[J].上海预防医学,2000;12(5):210
    [52] 李汝安,张颖.三七总甙片和祛风化痰通腑汤治疗高血压脑出血40例疗效观察[J].中西医结合实用临床急救,1992;4(1):514-515
    [53] 徐皓亮,等.三七皂甙Rg1对大鼠实验性血栓形成、血小板聚集率及血小板内游离钙水平的影响[J].中国药理学与毒理学杂志,1998;12(1):40-42
    [54] LiSH,Chu Y.Anti-inflammatory effects of total saponins of Panax notoginseng[J].Acta Phamacologica Sinica, 1999;20(6):551-554
    [55] 吉中强,等.11种中药对大鼠血小板聚集和红细胞流变性的影响[J].山东中医杂志,2000;19(2):107-108
    [56] 敬璞,等.柑桔皮渣提取小鼠体内的抗氧化作用研究[J].西南农业大学学报,2003;25(3):265
    [57] 叶任高.陆再英.内科学.6版.人民卫生出版社.2006:410。
    [58] 周燕红,等。大鼠溃疡性结肠炎超氧化物歧化酶和丙二醛的变化.咸宁学院学报(医学版).2003;17(6)391—393。
    [59] 陈文彬,等.诊断学.6版.人民卫生出版社.2005:339.
    [60] 贺国斌,欧阳钦,杨明辉,魏锦,溃疡性结肠炎患者凝血酶抗凝血酶复合物和D-二聚体检测,中华消化杂志,2004,24(7):438—439
    [61] 许丽莉,王吉耀,活动期溃疡性结肠炎患者体内血小板激活状态的评价,中华消化杂志,2002,22(5):285—287.
    [62] 徐德亮,穆平等,溃疡性结肠炎血液流变学及抗凝的临床研究,胃肠病学和肝病杂志,2005,14(4):413—415。
    [63] Carson DA, Ribeiro JM. Apoptosis and disease [J].Lancet, 1993,341:1251.
    [64] 徐细明,于皆平,何小飞,李军华,於亮亮,大蒜素对大鼠溃疡性结肠炎bcl-2、Bax蛋白表达的影响,医药导报,2003,22(12):835—838.
    [65] MacDonaldTT, MonteleoneG, PenderSL.Recent.developments.in.the.immunology.of.in flammatory, bowel, disease[J]..Scand J Immunol, 2000,51(1):229.
    [66] PapadakisKA, Targan.SR. Role. of. cytokines, in. the. pathogenesis, of. inflammatory. ..bowel. disease[J].Annu. Rev. Med, 2000, 51: 289-298.
    [67] ArdizzoneS, Porro. GB. Inflammatory. bowel, disease:new., insights, into. pathogenes is. and. treatment [J]. J. Int. Med, 2002. 252: 475-496.
    [68] 张可,等.溃疡性结肠炎组织中NF-kB,cox-2和iNOS表达的意义[J],世界华人消化杂志,2002,10(5):575—6。
    [69] 祝斌,等.溃疡性结肠炎患者周围血中性粒细胞凋亡与细胞因子水平的关系,临床消化病杂志,2003(6):254—256
    [70] J F Mouser, PhamD, J S Hyams. lnfliximab:a novel chimeric monoclonal antibody for the treatment of Crohn' s Disease Clinical Therapeutics, 1999,21(6):932-942.
    [71] 修宗昌,等.脾虚免疫学机制[J].中国中医药信息杂志.2003;10(4):10—13。
    [72] 靳文学,杨宇.从黏膜免疫系统看“肺与大肠相表旱”.四川中医.2005;23(12):1—3。
    [1] Eaden J,Abrams K,Ekbom A,Jackson E,Mayberry J.Colorectal cancer prevention in ulcerative colitis:a case-control study.Aliment Pharmacol Ther 2000; 14: 145-153
    [2] 中华医学会消化病学分会,对炎症性肠病诊断治疗规范的建议(2000年),现代实用医学,2003,15(10):656—659。
    [3] Orchard TR, Chua CN,Ahmad T, et,al,Uveitis and erythema nodosum in inflammatory bowel disease:clinical features and the role of HIA genes Gastroenterologuy,2002,123(3):714-8.
    [4] Christodoulou DK,Katsanos KH,Kitsanou M,et al,Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature,Dig Liver Dis,2002,34(11):718-6.
    [5] 陈灏珠,丁训节,廖履坦,等,实用内科学。人民卫生出版社,2001:1785—1789。
    [6] Farrokhyar F, Swarbrick ET, Irvine EJ.A critical review of epidemiological studies in inflammatory bowel disease.Scand J Gastroenterol,2001,36:2-15.
    [7] Morita N,Toki s,Hirohashi T, et al.Incidence and prevalence of inflammatory bowel disease in Japan:nationwide epidemiological survey during the year 1991. J Gastroenterol, 1995,30 (suppl 8): 1-4.
    [8] Tan CC,Kang JY, Guan R,et al.Inflammatory bowel disease:an uncommon problem in Singapore.J Gastroenterol Hepatol, 1992,7:360-362.
    [9] 中国炎症性肠病协作组,3100例溃疡性结肠炎住院病例回顾分析,中华消化杂志,2006年26(6):368—372。
    [10] 萧树东,消化系疾病基础与临床进展,上海科学技术文献出版社,2005:236
    [11] Sartor RB.Pathogenesis and immunemechanism of chronic inflammatory bowel disease.Am J Gastroenterol 1997;92(12Supple):S5-S11.
    [12] 徐保平,王伟岸.消化系疾病免疫学.北京:科学出版社,2000:52—53。
    [13] Campieri M,Gionchetti P.Bacteria as the cause of ulcerative colitis.Gut 2001 ;48:132-135
    [14] Eggena M,Cohavy O,Parseghian MH,Hamkalo BA,Clemens D,Targan SR,Gordon LK,Braun J.Identification of hidtone H1 as a cognate antigen of the ulcerative colitis-associated marker antibody pANCN.J Autoimmun 2000; 14:83-97
    [15] Gordon LK,Eggena M,Targan SR,Braun J.Mast cell and neuroendocrine cytoplasmic autoantigen(s) detected by monoclonal pANCA antibodies.Clin Immunol 2000;94:42-50
    [16] Gordon LK,Eggena M Targan SR,Braun J.Definition of ocular antigens in ciliary body and retinal ganglion cells by the marker antibody pANCA.Invest Ophthalmol vis Sci 1999;40:1250-1255
    [17] Cohavy O,Bruckner D,Gordon LK,Misra R, Wei B,Eggena ME,Targan SR,Braun J.Colonic bacteria express an ulcerative colitis pANCA-related protein epitope.Infect Immun2000;68:1542-1548
    [18] MacDonald NJ,Shivers WY, Narum DL,Plum SM,Wingard JN,Fuhrmann SR,liang H,Holland-Linn J,Chen DH,Sim BK.Endostatin binds tropomyosin.A potential modulator of the antitumor activity of endostatin.J Biol Chem 2001;276:25190-25196
    [19] Taniguchi M,Geng X,Glazier KD,er al,Cellular immune response against tropomyosin isoform 5 in ulcerative colitis[J].Clin Immunol,2001,101:289-295
    [20] Vashishtha A,Fischetti VA.Surface-exposed conserved region of the streptococcal M protein induces antibodies crossreaction with denatured forms of myosin.J Immunol 1993; 150:4693-4701
    [21] Xu CT, Meng SY, Pan BR.Drug therapy for ulcerative colitis[J].World J Gastroenterol,2004,10(16): 2311-2317
    [22] Eaden J,Abrams K,Ekbom A,et al.Colorectal cancer prevention in ulcerative colitis:a case-control study [J].Aliment Pharmacol Ther,2000,14:145153
    [23] Russel MG.Changes in the incidence of inflammatory bowel disease:what does it mean[J] Eur J Intern Med,2000,11:191-196
    [24] Taniguchi M,Geng X,Glazier KD,et al.Cellular immune response against tropomyosin isoform 5 in ulcerative colitis[J].Clin Immunol,2001,101:289-295.
    [25] Yacyshyn BR.Antisense oligonucleotide treatment of inflammatory bowel diseases.Methods Mol Med,2004,106:295-306.
    [26] Laroux Fs,Pavlick KP, Wolf RE,et al.DysreguIation of intestinal mucosal immunity:implications in inflammatory bowel disease[J],News Physiol Sci,2001,16:272-277
    [27] Dejica D.Serum soluble IL-2 receptor as a marker of lymphocyte activation in some autoimmune diseases.Effect of immunosuppressive therapy[J].Roum Arch Microbiol Immunol, 2001,60:183-201.
    [28] Lim WC,Hanauer SB.Controversies with aminosalicylates in inflammatory bowel disease[J].Rev Gastroenterol Disord,2004,4(3): 104-107.
    [29] Hanauer SB.Review article:the long-term management of ulcerative colitis[J].Aliment Pharmacol Ther,2004,20(suppl 4):97-101.
    [30] Dasgupta A,Mandal A,Das M.Circulating immunoglobulin G_1 antibody in patient with ulcerative colitis against the colonic epithelial protein detected by a novel monoclonal antibody.Gut, 1994,35(12): 1712-1717
    [31] 余保平,王伟岸主编.消化系疾病免疫学.科学出版社.北京.2002.3—7
    [32] 郑萍,陈胜良,莫剑忠,罗鸿妤,炎症性肠病患者T淋巴细胞亚群的改变及临床意义,胃肠病学,2000,5(4):220—222
    [33] 王巧民,翟志敏,等,溃疡性结肠炎T淋巴细胞亚群检测及其意义,中华消化杂志,2002,22(6):366—367。
    [34] 蒋维国,徐华,溃疡性结肠炎患者外周血T细胞亚群检测及其意义,中国肛肠病杂志,1997,11(2):85。
    [35] 祁红,马红,溃疡性结肠炎患者外周血T细胞亚群和免疫球蛋白分析,辽宁医学杂志,1997,11(2):85
    [36] Lim WC,Hanauer SB.Controversies with aminosalicylates in inflammatory bowel disease[J].Rev Gastroenterol Disord,2004,4(3): 104-107.
    [37] Hanauer SB.Review article:the long-term management of ulcerative colitis[J].Aliment Pharmacol Ther,2004,20(suppl 4):97-101.
    [38] MacDonaldTT,MonteleoneG,PenderSL.Recent.developments.in.the.immunology.of.inflammatory.bowel.disease[J]..Scand J Immunol,2000,51 (1):229.
    [39] PapadakisKA,Targan.SR.Role.of.cytokines.in.the.pathogenesis.of.inflammatory...bowel.disease [J].Annu.Rev.Med,2000,51:289-298.
    [40] ArdizzoneS,Porro.GB.Inflammatory.bowel.disease:new..insights.into.pathogenesis.and.treatment[J].J.Int.Med,2002.252:475-496.
    [41] 卢艺涛,高静,姚桂琴,溃疡性结肠炎患者相关细胞因子的试验性研究。现代预防医学,2005,32(7):735—736
    [42] 李琪佳,宫恩聪,刘叔平,鄂文.溃疡性结肠炎黏膜的白细胞亚群和肿瘤坏死因子—α的表达.临床与实验病理学杂志,2001,17(3):216—218
    [43] 张可,邓长生,朱尤庆,溃疡性结肠炎组织中NF-kB,cox-2和iNOS表达的意义[J],世界华人消化杂志,2002,10(5):575—6。
    [44] 祝斌,李巧勤,陈垦,徐军发,陈小芳,溃疡性结肠炎患者周围血中性粒细胞凋亡与细胞因子水平的关系,临床消化病杂志,2003(6):254—256
    [45] J F Mouser, PhamD,J S Hyams.Infliximab:a novel chimeric monoclonal antibody for the treatment of Crohn's Disease Clinical Therapeutics, 1999,21 (6):932-942.
    [46] Bonizzi G, Karin M. The two NF-kB activation pathways and their role in innate and adaptive immunity. Trends Immunol2004;25:280-288
    [47] AshwoodP, HarveyR,VerjeeT.Functional interactions between mucosal IL-1,IL-1ra and TGF-beta 1 in ulcerative colitis[J].Inflamm Res,2004,53(2):53
    [48] Schottelins AJ,Baldw in AS. A role for transcription factor NF-kappaB in intestinal inflammation[J].Int J Colorectal Dis, 1999,14:18
    [49] Stevens C,Walz G, Singaram C,et al.Tumor Necrosis Factor-α Interleukin-1β, and Interleukin-6 Expression in inflammatory Bowel Disease.Digestive Diseases and Sciences.1992,37:818~826.
    [50] 丁伟群,林庚金,徐三荣,等.溃疡性结肠炎发病中白介素水平的变化.复旦学报(医学科学版),2001,28(4):330.
    [51] HolubMC,MakoE,DebayT,etal.Increasedinter-leukin-6isrelatedtodisease.JClinGastroenterol, 1995,20:123.
    [52] Grotup-Wolfers E,MoellerJ,Karbach U,et al.Elebate cell-associated levels of interleukin1β and interleukin-6 in inflamed mucosa of inflammatory bowel disease. Eur H Cli Invest 1996,26:115.
    [53] Imada A,Ina k.Shimada M,et al.Coordinate upregulation of interleukin-8 and growth-related gene product-alpha is present in the colonic mucosa of inflammatory bowel[J].Scand J Gastroenterol,2001,36(8):854
    [54] HaiYZ,Satoru Mineshita.The effect of berberine chloride on experimental colitis in rats in vivo and in vitro[J]. J Pharm and ExpThera,2000,294(3):822
    [55] Kwshavarzian A,Fusunyan RD,Jacyno M,et al.Increased interleukin-8(IL-8) in rectal dialysate from patients with ulcerative colitis:evidence for a biol-ogical role for IL-8 in inflammation of the colon[J],Am J Gastroenterol, 1999,94(3):704
    [56] Gasche C,Bakos S,Dejaco C,et al.IL-10 secretion and sensitivity in normal human intestine and inflammatory bowel disease.J Clin Immunol,2000,20:362.
    [57] Autschbach F, Braunstein J,Helmke B,et al.In situ expression of interleukin-10 in noninflamed human gut and in inflammatory bowel disease.Am J Pathol, 1998,153:121.
    [58] Akagi S,Hiyama E,Imamura Y, et al.Interleukin-10 expression in intestine of Grohn disease. Int J Mol Med 2000,5:389.
    [59] 陈维雄,陈金联,陈尼维,朱金水,达炜,P选择素单抗对小鼠溃疡性结肠炎治疗的研究,中华消化杂志,2001,21(10):629—630
    [60] 徐军发,吕世静,祝斌,溃疡性结肠炎患者血浆P—选择素和白细胞介素—8的检测及临床意义,中国肛肠病杂志,2002,22(7):6—8
    [61] 沈洪,等.调理脾肺法对实验性大鼠溃疡性结肠炎作用机理的研究.江苏中医药.2002;23(12):53—54.
    [62] 乔为平,等.固本保元浸膏敷脐对溃疡性结肠炎大鼠自由基和过氧化脂质的影响.贵阳中医学院学报.1999;21(4):58—59.
    [63] 焦君良,等.溃疡性结肠炎血清免疫学及SOD活性变化.河北医药.2000;22(7):497—498.
    [64] 黄俊,等.大鼠实验性溃疡性结肠炎中NO、MDA、SOD的变化.武汉大学学报(医学版).2002;23(2):146—148.
    [65] 周燕红,刘毅飞.姜黄素对溃疡性结肠炎脂质过氧化损伤大鼠的保护作用.咸宁学院学报(医学版).2005;19(4):280—282.
    [66] 王少华,等.丹参对大鼠溃疡性结肠炎SOD活性和MDA含量影响的实验研究[J].中国肛肠病杂志.2000;20(7):3.
    [67] Nielsen OH,Ahnfelt-Ronne I.Involvement of oxygenderived free radical in the pathogenesis of chronic inflammatory bowel disease[J].Klin Wochenschr, 1991;69(21-23):995.
    [68] 季雁浩,等.肠安宁治疗溃疡性结肠炎的机理研究.上海中医药杂志.2005;39(4):53—55.
    [69] 王献坤,等.肠安康对大鼠溃疡性结肠炎的治疗作用及机理探讨.北京中医药大学学报.2004;27(4):31—34.
    [70] 贺国斌,欧阳钦,杨明辉,魏锦,溃疡性结肠炎患者凝血酶抗凝血酶复合物和D-二聚体检测,中华消化杂志,2004,24(7):438—439
    [71] 许丽莉,王吉耀,活动期溃疡性结肠炎患者体内血小板激活状态的评价,中华消化杂志,2002,22(5):285—287.
    [72] 徐德亮,穆平等,溃疡性结肠炎血液流变学及抗凝的临床研究,胃肠病学和肝病杂志,2005,14(4):413—415。
    [73] 张连峰,田曙光,王国新.溃疡性结肠炎患者血小板功能状态的研究,中国实用内科杂志,2000,20(2):98299.
    [74] Laissue JA,Chappuis BB,Muller C,Reubi JC,Gedders JO,The intestinal immune system and its relation to disease.Dig Dis 1993;11:298-312
    [75] Harari Y, Weisbrodt NW, Moody FG. Ileal mucosal response to bacterial toxin challenge.J Trauma 2000;49:306-313
    [76] Kiyono H,Kweon MN,Hiroi T, Takahashi I.The mucosal immune system:from specialized immune defense to inflammation and allergy.Acta Odontol Scand 2001 ;59:145-153
    [77] 李宁.肠屏障功能障碍及我们的对策.中国实用外科杂志2000;20:35—36
    [78] Nusrat A, Turner JR,Madara JL. Molecular physiology and pathophysiology of tight junctions.Ⅳ Regulation of tight junctions by extracellular stimuli:nutrients,cytokines,and immune cells.Am J Physiol Gastrointest liver Physiol 2000;279:G851-G857
    [79] Colgan SP, Dzus AL,Parkos CA.Epithelial exposure to poxia modulates neutrophil transepithelial migration.J Exp Med 1996; 184:1003-1015
    [80] Muller S,Lory L,Corazza N C,et al.Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease.Am J Pathol, 1998,152:261-268.
    [81] Carson DA,Ribeiro JM.Apoptosis and disease [J].Lancet, 1993,341:1251.
    [82] 冯建芳,章静波。程序性细胞死亡及细胞凋亡。生理科学进展1995,26:373—378。
    [83] 彭远英,彭正松,喻可芳。凋亡细胞的超微结构变化。细胞生物学杂志2003,25:280—283。
    [84] 刘丽芳,吴人亮,吴翠环。细胞胀亡(oncogenisis):一种不同于凋亡(apoptosis)的死亡方式。国外医学分子生物学分册 2002,24:285—288。
    [85] Tsujimoto Y, Shimizu S.Bcl-2 family:life-or-death switch.FEBS Lett2000,466:6-10.
    [86] Yinn XM,01tval ZN,Korsmeyer SJ.BH1 and BH2 domains of Bcl-2 ate rewuires for inhibition of apoptosis and heterodimerization with Bax.Nature 1994,369:321-323.
    [87] Zhang L,Yu J,Park BH,et al.Role of BAX in the apoptotic response to anticancer agents.Science 2000,290:989-992.
    [88] 徐细明,于皆平,何小飞,李军华,於亮亮,大蒜素对大鼠溃疡性结肠炎bcl-2、Bax蛋白表达的影响,医药导报,2003,22(12):835—838.
    [89] 吴焕淦,黄臻,刘慧荣,张卫,施茵,朱毅,崔云华,刘世敏,针灸对大鼠溃疡性结肠炎结肠上皮细胞凋亡影响的试验研究,中国针灸,2005,25(2):119—122
    [90] 薛筠,谢建群,清肠栓对溃疡性结肠炎大鼠结肠上皮凋亡影响的流式细胞术研究,上海中医药大学学报,2005,19(3):42—44
    [91] 徐细明,于皆平,何小飞,李军华,於亮亮,大蒜素对大鼠溃疡性结肠炎bcl-2、Bax蛋白表达的影响,医药导报,2003,22(12):835—838.
    [92] 范恒,邱明义,梅家俊,沈关心,刘松林。理肠中药方对溃疡性结肠炎大鼠结肠细胞凋亡及其凋亡基因表达的影响。世界华人消化杂志,2004,12(5):1199—1124。
    [93] Iimura M,Nakamura T, Shinozakis,et al.Bax is downregnlated in inflamed colonic mucosa of ulcerative colitis,Gut,2000,47:228-235.
    [94] Persson PG, AhIbom A,Hellers G, Inflammatory bowel disease and tobacco smoke a case contral study, Gut,1990,31; 1377-1381.
    [95] Russel MG, Engels L G, Muris JW, et al, "Modem life" in the epidemiology of inflammatory bowel disease: a case-control study with special emphasis on nutritional factors,Eur J Gastroenterol Hepatol, 1998, 10; 243-249
    [96] 袁岸龙,夏冰,李瑾,等,湖北地区溃疡性结肠炎患者生活习惯的研究,中华消化杂志,2003,23(4):245—246
    [97] 刘凤芹,楚更五,李子华,等,心理因素与溃疡性结肠炎,健康心理学杂志,2001,9(4);306—307。
    [98] Campitri M.Gut,2002;50(Supp13):43-46.
    [99] Kruisa W, Schreiberb S,Theuerc D,et al.Gut,2001 ;9(6):783-789.
    [100] Levine DS,Rift DS,Pruitt R,et al.Am J Gastroenterology,2002 ;97(6): 1398-1407
    [101] Marshall JK,Irvine EJ.AM J Gastroenterol.2000;95(7): 1628-1636
    [102] Okarnura S,Aoki H,Ohashi S,et al.Hepatogstroenterology,2003 ;50(49):91-94
    [103] D Haens G, Lemmens L,Geboes K.etal.Gastroenterology,2001 ;120(6):1323-1329
    [104] Ghosh S,Shand A,Ferguson A.BMJ,2000;320(7242): 1119-1123
    [105] 王晓兰,吕和平,康跃军.肿瘤坏死因子α与炎症性肠病研究进展[J].洛阳医专学报,2002,20(3):264—265.
    [106] Schultz M. [J].Gastroenterology, 1998,114(4Pt2):A 1081.
    [107] Dieleman LA, Goerres M S,Arends A, et all[J].Gut,2003,52(3):370-376.
    [108] KruisW, Schutz E, Fric P, et al [J]. Alimen Pharmacol T her,1997,11(5):853-858.
    [1] 杨晔.溃疡性结肠炎.当代内科学.北京:中国中医药出版社.2002:2672-2673
    [2] 张正利.蔡淦.溃疡性结肠炎中医治疗及理论探讨.陕西中医.2001;22(7):405—406
    [3] 段荣章.慢性溃疡性结肠炎从肝论治.河南中医.1996;16(6):342
    [4] 张理,黄发盛.宏观与微观结合论治溃疡性结肠炎血瘀证.光明中医.2004;19(4):21—23
    [5] 焦君良,要丽瑛,李士军,刘桂缺.从痈论治溃疡性结肠炎初探.中国中西医结合脾胃杂志.2000;8(2):100—101
    [6] 沈洪,等.调理脾肺法对实验性大鼠溃疡性结肠炎作用机理的研究.江苏中医药.2002;23(12):53—54
    [7] 杨静.中医辨证治疗溃疡性结肠炎64例.陕西中医.2003;24(7):616—617
    [8] 李向辉,毛秉豫,韩珂.溃疡性结肠炎的中医辨证分型综合治疗.中华实用中西医杂志.2004;4(17):3558—3559
    [9] 程卫军.疏肝健脾法治疗溃疡性结肠炎的临床观察.中国中西医结合杂志.2001;21(1):34—36
    [10] 吴惠珍.补脾固肾法治疗慢性溃疡性结肠炎38例.四川中医.2001;19(12):23—24
    [11] 范淑惠,胡筱娟.活血化瘀辨证治疗慢性溃疡性结肠炎.实用中医内科杂志.1991;5(4):23—24
    [12] 席作武.活血化瘀法治疗溃疡性结肠炎82例.中国中西医结合脾胃杂志,2000,8(3):161—162
    [13] 卞耀臣,李振武.温里化痰法治疗慢性溃疡性结肠炎60例.山东中医杂志.2004;23(8):472
    [14] 张永艳.宣肺健脾汤治疗慢性溃疡性结肠炎68例.河北中医.2000;22(8):599—600
    [15] 卢涛.葛根黄芩黄连汤加味治疗慢性非特异性溃疡性结肠炎32例疗效观察.新中医.2000;32(10):19—20
    [16] 张燕,王翔燕,张富平.芪菊饮对溃疡性结肠炎患者CD_(44)和CD_(54)的影响.实用中医内科杂志.2004;18(5):453—54
    [17] 周秦汉,俞军,谷淑玲.速效溃结散保留灌肠治疗慢性非特异性溃疡性结肠炎临床与实验研究.中国中西医结合杂志.1999;19(7):395—398
    [18] 陈雪清,陈小华,高记华.三黄汤加减保留灌肠治疗溃疡性结肠炎76例.中华实用中西医杂志.2004;4(17):990—991
    [19] 王梅青,徐志峰,冯江雪.西黄合剂保留灌肠治疗溃疡性结肠炎50例临床观察.中华实用中西医杂志.2004;4(17):996—997
    [20] 李国珍.中药灌肠治疗溃疡性结肠炎的中医护理.护士进修杂志.1999;14(6):53
    [21] 史亚祥.肠愈Ⅰ号冲剂和祛疡散治疗溃疡性结肠炎128例.中国中西医结合杂志.2002:22(5):392—393
    [22] 苏路侠,王守才.中药口服及灌肠治疗慢性非特异性溃疡性结肠炎124例.中国中药杂 志.2002;27(9):706—708
    [23] 张友安.中药口服与灌肠治疗慢性溃疡性结肠炎活动期73例.陕西中医.2002;23(1):34—35
    [24] 顾月星,徐大龙,李国安.中西药联合灌肠治疗慢性溃疡性结肠炎44例.中国中西医结合杂志.2001;21(7):544
    [25] 陈全寿,张汉臣.中西医结合治疗溃疡性结肠炎118例.中国中西医结合杂志.1999;19(7):398
    [26] 海正星,罗万成,丁成福.中西医结合治疗溃疡性结肠炎124例.陕西中医.2001;22(7):397
    [27] 郭俊山.肠疡散配合电针治疗慢性非特异性溃疡性结肠炎.中华实用中西医杂志.2004;4(17):2745
    [28] 杨晨曦,张凤娥,苏筱玲.电热针结合艾灸中药治疗溃疡性结肠炎疗效观察.中国针灸.2004;24(4):238—240
    [29] 张新唯.艾灸治疗溃疡性结肠炎55例.中国针灸.2001;21(4):198
    [30] 杨振辉,张悦,孙英霞.针刺央脊穴配合梅花针叩刺治疗溃疡性结肠炎疗效观察.中国针灸.2003;23(3):141—142
    [31] 陈杰.特定穴埋线治疗慢性非特异性溃疡性结肠炎临床观察.四川中医.2004;22(5):89—90
    [32] 朱莹,袁伟建,姚红艳.穴位埋线对溃疡性结肠炎患者血清IL-2受体及T淋巴细胞亚群的影响.中国中西医结合杂志.2003;23(1):58—59
    [33] 叶新苗,阮继源,张光霁.仿穴位注射治疗慢性溃疡性结肠炎21例.中国针灸.2003,;23(9):536
    [34] 冯国湘,吴清明,陈松.痛泻宁穴位贴敷治疗溃疡性结肠炎临床观察.中国针灸.2002;22(5):312—314

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700