两种短程疗法治疗幽门螺杆菌阳性胃及十二指肠溃疡对照研究

枸橼酸铋钾在胃液酸碱条件下，在溃疡表面或溃疡基地肉芽组织形成一种坚固的氧化铋胶体沉淀，成为保护膜，从而隔绝胃酸酶及食物对溃疡黏膜的侵蚀作用：刺激内源性前列腺素释放，促进溃疡组织的修复和愈合，还能改善胃黏膜血流与清除幽门螺杆菌（Hp）的作用。为了评价枸橼酸铋钾与雷尼替丁合用根除Hp阳性的胃及十二指肠溃疡的疗效与安全性，我们对枸橼酸铋钾雷尼替丁三联疗法与奥美拉唑三联疗法治疗Hp阳性的胃及十二指肠溃疡疗效进行对照观察。现总结报告如下。     

巯基物质对小剂量阿司匹林所致大鼠胃黏膜损伤的保护作用

背景：很多胃黏膜损伤模型中发现巯基物质含量下降，巯基物质对胃黏膜细胞具有保护作用。目的：探讨巯基物质对小剂量阿司匹林所致胃黏膜损伤的保护作用。方法：80只雄性Sprague-Dawley（SD）大鼠随机分为正常对照组、纯巯基对照组、阿司匹林模型组、巯基预防组、硫糖铝预防组、NaCl治疗对照组、巯基治疗组和硫糖铝治疗组8组。测定黏膜溃疡指数（UI），行大体、组织学和透射电子显微镜观察，测定胃黏膜组织中还原型谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、丙二醛（MDA）、6-酮．前列腺素F1α（6-keto-PGF1α）水平。结果：阿司匹林模型组胃黏膜发生病变，UI与其余各组相比显著升高（P〈0．01），GSH、6-keto-PGF1α含量较正常对照组显著降低（P〈0．05），MDA含量显著增高（P〈0.001）。巯基预防或治疗后，胃黏膜损伤明显减轻，UI显著下降（P〈0．001），GSH、6．keto．PGF1α含量显著增高（P〈0．05），MDA含量显著降低（P〈0．05）。各组SOD含量无显著差异。结论：小剂量阿司匹林可致大鼠胃黏膜损伤，胃黏膜GSH下降可能是其机制之一。外源性GSH具有增强胃黏膜抗氧化作用和细胞保护作用。     

成纤维细胞生长因子在保护胃和溃疡愈合中的作用:与硫糖铝的相互作用

成纤维细胞生长因子(FGF)有酸性和碱性两种形式。有报道口服碱性FGF(bFGF)可加速乙酸或半胱氨诱发大鼠胃、十二指肠溃疡的愈合。本研究目的为确定人的重组bFGF与胃粘膜和溃疡的结合;测定bFGF对多种刺激物质和应激所致粘膜损害的保护活性;其在胃溃疡愈合中的效果,以及在保护胃粘膜及胃溃疡愈合中与硫糖铝的相互作用。 结果发现:1.皮下输注bFGF1～100μg/kg·h或100μg/kg灌胃对胃酸和胃蛋白酶的分泌均无显著影响。2.上述剂量的bFGF不能减轻纯酒精或酸化阿斯匹林引起的急性胃粘膜病变,也不提高病变粘膜的血流量;预先或同时应用硫糖铝灌胃可减少粘膜病变面积并提高粘膜血流量。而对应激性急性胃粘膜病变,不但硫糖铝可减少病变面积和增加血流量,皮下输注bFGF也可减轻其损伤,两者合用有协同作用,但     

六君子加减方对大鼠胃溃疡黏膜组织生长因子的影响

[目的]观察六君子加减方对溃疡大鼠胃黏膜表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）水平的影响，进一步探讨其可能的作用机制。[方法]32只雄性Waistar大鼠，8只作为正常对照（正常）组，24只采用Okabe乙酸烧灼法在大鼠胃前壁造成溃疡模型，随机分为模型对照（模型）组、六君子加减方（六君子方）组、硫糖铝组，每组8只，各组分别连续给药治疗10d。给药结束后，定量检测溃疡周围组织EGF和bFGF的水平。[结果]模型组大鼠胃组织EGF及bFGF的水平明显高于正常组（P〈0．01）；六君子方组胃组织EGF及bFGF的水平低于模型组（P〈0．05），而与正常组和硫糖铝组比较，差异均无统计学意义（P〉0．05）。[结论]中药六君子加减方可能通过对胃组织EGF及bFGF水平的调控而促进损伤后黏膜的愈合，可能是其作用机制之一。     

复方尿囊素片对乙醇所致大鼠胃黏膜损伤保护作用的实验研究

目的研究复方尿囊素片对乙醇所致大鼠急性胃黏膜损伤的预防保护作用及其机制。方法 60只健康雄性Wistar大鼠随机分为5组：乙醇损伤组、空白对照组、硫糖铝保护组、氢氧化铝保护组、复方尿囊素保护组。保护组分别用硫糖铝、氢氧化铝及复方尿囊素片提前给大鼠灌胃,其后用乙醇灌胃致急性胃黏膜损伤,然后分别测定各组胃黏膜溃疡指数、黏膜损伤积分、胃黏膜血流、黏膜前列腺素E2（PGE2）及一氧化氮（NO）含量,并在显微镜及电镜下观察胃黏膜组织学改变。结果复方尿囊素保护组的各项检测指标显示：溃疡指数、损伤积分显著低于乙醇损伤组（P=0.000,P=0.000）,明显低于氢氧化铝保护组（P=0.020,P=0.004）,也低于硫糖铝保护组,但差异无统计学意义（P=1.000,P=1.000）;黏膜血流值较乙醇损伤组明显增加（P=0.000）,明显高于氢氧化铝保护组（P=0.019）,与硫糖铝保护组的差异无统计学意义（P=0.266）;黏膜PGE2及NO含量均较乙醇损伤组明显增加（P=0.000,P=0.001）,明显高于氢氧化铝保护组（P=0.002,P=0.001）,也高于硫糖铝保护组,但差异无统计学意义（P=0.451,P=0.199）。结论复方尿囊素片对乙醇所致大鼠急性胃黏膜损伤有明显的预防保护作用,其作用是通过增加胃黏膜血流、增加黏膜PGE2及NO含量等机制实现的。     

莫沙必利对阿司匹林致大鼠急性胃黏膜损伤的保护作用

研究显示促胃肠动力药物莫沙必利对胃黏膜损伤具有一定的保护作用。目的：研究不同剂量莫沙必利对阿司匹林致大鼠急性胃黏膜损伤的保护作用及其机制。方法：将50只大鼠随机分为阴性对照组、单纯损伤组以及不同剂量莫沙必利干预组（0．25mg／kg、0．50mg／kg、0．75mg／kg）。干预组大鼠以不同剂量莫沙必利灌胃行预处理,以150mg／kg阿司匹林灌胃制备急性胃黏膜损伤模型。实验第4d,处死大鼠。评估大鼠胃黏膜损伤指数和组织学变化,以免疫组化法检测Occludin蛋白分布,蛋白质印迹法检测Occludin、ZO．1以及磷酸化ERK（p-ERK）、磷酸化JNK（p-JNK）和磷酸化p38（p-p38）蛋白表达。结果：与单纯损伤组相比,各莫沙必利干预组胃黏膜损伤指数均明显降低（P〈0．05）;胃黏膜组织学明显改善;胃黏膜Occludin、ZO-1蛋白表达呈剂量依赖性升高（P〈0．05）;胃黏膜p-ERK、p-p38蛋白表达呈剂量依赖性降低（P〈0．05）;而胃黏膜p-JNK蛋白表达无明显差异。结论：莫沙必利对阿司匹林致大鼠急性胃黏膜损伤具有明显保护作用,其机制可能为降低MAPKs信号通路中ERK和p38蛋白磷酸化程度,并上调胃黏膜紧密连接蛋白Occludin和ZO-1表达,从而改善胃黏膜屏障的功能。     

消化性溃疡的病因及药物治疗并文献资料复习

消化性溃疡是我国人群中常见病之一，各种因素如幽门螺杆菌感染、药物、遗传及社会心理因索等均可诱发或促进本病的发生。组胺H2受体拈抗剂（如法莫替丁）、质子泵抑制剂（如奥美拉唑）、抗酸分泌药物与胃黏膜保护剂（如硫糖铝混悬液、胶态次枸橼酸铋）等联合应用可有效地治疗消化性溃疡病。应用奥美拉唑、阿莫西林及克拉霉素三联7天治疗可有效地根治幽门螺杆菌和促进溃疡愈合。     

生长因子保护胃十二指肠及促进消化性溃疡愈合的作用

急性或慢性消化性溃疡是由损害因素和保护因素失衡所引起。消化性溃疡的愈合既可以通过减少损害因素,也可以通过加强粘膜保护因素。由于消化性溃疡是粘膜的特殊损伤,因而,坏死组织脱落的同时,刺激未分化表皮细胞生长的作用应被看作愈合过程的重要因素。文献报告,具有营养作用的表皮生长因子(epi-dermal growth factor,EGF)或胃泌素刺激粘膜生长,促进再上皮化和组织修复。硫糖铝、枸橼酸铋钾等药物可增加溃疡区域EGF的聚     

胃黏膜保护剂与急性胃黏膜病变

一、急性胃黏膜病变的概念和发生机制 急性胃黏膜病变（acute gastric mucosal lesion，AGML）又称应激性溃疡，是指机体在各类严重创伤、危重疾病、严重心理应激或各类损害胃黏膜的药物（如阿司匹林、乙醇等）作用下所引起的上消化道急性糜烂、溃疡，主要表现为上消化道出血，少数可并发穿孔。不同病因引起AGML的发生机制不尽相同，一般认为胃酸增加、胃肠黏膜缺血和胃黏膜屏障功能削弱是发生AGML的关键因素。其发生机制主要涉及以下几个方面：①胃内酸度改变及逆流入黏膜内的H^＋增加；     

马来酸伊索拉定对阿司匹林所致大鼠胃黏膜损伤的保护作用

目的探讨马来酸伊索拉定对阿司匹林所致大鼠胃黏膜损伤的保护作用及其机制。方法 60只健康雄性Wistar大鼠随机分成5组:空白对照组、阿司匹林损伤组、马来酸伊索拉定保护组、硫糖铝保护组、奥美拉唑保护组。各保护组分别用马来酸伊索拉定(10 mg/kg)、硫糖铝(600 mg/kg)及奥美拉唑(10 mg/kg)提前给大鼠灌胃,阿司匹林损伤组用生理盐水(9 mg/ml)灌胃,再用阿司匹林(150 mg/kg)灌胃致急性胃黏膜损伤,测量各组胃黏膜溃疡指数(UI)、黏膜损伤积分(EDS)、胃黏膜血流值、一氧化氮(NO)、氨基己糖、白介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)的含量,并在显微镜及电镜下观察胃黏膜组织学改变。结果马来酸伊索拉定保护组各项检测指标显示:UI、EDS明显低于阿司匹林损伤组(P0.01),高于奥美拉唑保护组(P0.05),略低于硫糖铝保护组(P0.05);胃黏膜血流值明显高于阿司匹林损伤组和硫糖铝保护组(P0.05),略低于奥美拉唑保护组(P0.05);NO含量明显高于阿司匹林损伤组(P0.01)和奥美拉唑保护组(P0.05),略低于硫糖铝保护组(P0.05);氨基己糖含量明显高于阿司匹林损伤组(P0.01),低于奥美拉唑保护组(P0.05),略高于硫糖铝保护组(P0.05);IL-1、TNF-α含量明显低于阿司匹林损伤组、奥美拉唑保护组及硫糖铝保护组(P0.01)。结论马来酸伊索拉定可以增加胃黏膜血流、NO及氨基己糖含量,同时抑制炎症性细胞因子IL-1、TNF-α的产生,对阿司匹林所致大鼠急性胃黏膜损伤有明显的预防保护作用。     

Fibroblast growth factor in gastroprotection and ulcer healing: interaction with sucralfate.

The study was designed to determine the gastroprotective and ulcer healing efficacy of basic transforming growth factor (bFGF) and to assess whether this peptide contributes to the action of sucralfate on the rat stomach. Application of human recombinant bFGF (1-100 micrograms/kg/hour subcutaneously) failed to affect the formation of acute gastric lesions induced by 100% ethanol and acidified aspirin but reduced the stress induced by gastric lesions. Sucralfate (100-200 mg/kg given orally) protected gastric mucosa against the ethanol, aspirin, and stress induced acute gastric lesions but the addition of bFGF (100 micrograms/kg subcutaneously or intragastrically) failed to affect sucralfate induced protection against ethanol or aspirin but increased that against stress. Administration of bFGF (3-300 micrograms/kg/day) by an intragastric or an intraperitoneal route or sucralfate (400 mg/kg/day) orally to rats with acetic acid induced gastric ulcers, enhanced the healing rate of these ulcers during seven day treatment in a dose dependent manner. This was accompanied by a pronounced increase in the number of capillaries and myofibroblasts and in DNA synthesis and DNA and RNA concentrations in the granulation tissue in the ulcer area. [125I]bFGF (1 microCi) applied subcutaneously or intragastrically accumulated in two to threefold higher amounts in the ulcer area than in the intact mucosa, particularly in rats treated with sucralfate. Concurrent treatment with indomethacin (2 mg/kg intraperitoneally) delayed ulcer healing and reduced the binding of labelled bFGF to the ulcer area, angiogenesis, and DNA synthesis by sucralfate. Addition of [125I]bFGF to sucralfate at various pHs resulted in the coprecipitation of bFGF by sucralfate in a pH dependent manner from about 10% at pH 7.0 to 90% at pH 1.5. Thus bFGF shows little protective activity and is not essential for gastroprotection afforded by sucralfate but plays an important part in healing of gastric ulcers possibly due to its growth promoting and angiogenic actions.     

黏膜保护剂对实验性胃黏膜损伤及胃黏膜超微结构改变的作用

目的 评价铝碳酸镁等常用黏膜保护剂对乙醇、阿司匹林、盐酸、泼尼松龙诱发的大鼠胃黏膜损伤的保护作用,并观察铝碳酸镁的黏膜保护作用与胃黏膜上皮细胞间隙变化的关系.方法 采用四种方法造模.①乙醇造模:采用雄性Wistar大鼠84只,分为7组,每组12只,分别给予铝碳酸镁、麦滋林、替普瑞酮、吉法酯、硫糖铝、瑞巴派特、0.9%氯化钠溶液3 d,第4天动物在给药后再经口给予无水乙醇l ml造模.之后处死动物观察药物对大鼠胃黏膜损伤的作用.计算各组胃黏膜损伤长度(mm)作为损伤指数.②阿司匹林造模:经口给予阿司匹林(300 mg/kg)及0.1 mol/L盐酸0.5 ml/100 g造模,余实验方法同①.③盐酸造模:经口给予0.7 mol/L盐酸1 ml造模,余实验方法同①.④泼尼松龙造模:动物分组及给药剂量同其他模型,给药或0.9%氯化钠溶液5 d,第2～5天每天皮下注射泼尼松龙(250 mg/kg),第5天处死动物,用Guth法计算损伤指数.取每种动物模型对照组及铝碳酸镁组的第1、5和10号动物胃黏膜组织,用透射电镜检测细胞间隙的变化.结果 四种胃黏膜损伤模型中,各黏膜保护剂用药组胃黏膜损伤指数均显著小于对照组(P值均＜0.05),其中铝碳酸镁组与对照组比较差异有统计学意义(P＜0.01).同时铝碳酸镁组胃黏膜上皮细胞间隙显著小于对照组(P＜0.05).结论 六种常用黏膜保护剂对乙醇、盐酸、阿司匹林、泼尼松龙诱发的胃黏膜损伤均有保护作用,其中铝碳酸镁的保护作用更显著.观察胃黏膜上皮细胞间隙可从细胞学水平进一步证实铝碳酸镁的黏膜保护作用.     

Prostaglandins in pathophysiology of peptic ulcer disease

Gastric ulcer (GU) and duodenal ulcer (DU) occur as a result of the imbalance between aggressive and defensive factors affecting the gastroduodenal mucosa. Prostaglandins (PG) of E and I series are generated throughout the gastrointestinal tract, particularly in the gastric and duodenal mucosa, and are released into the gut lumen upon vagal and hormonal stimulation. Endogenous PGs may be involved in the maintenance of mucosal integrity, control of mucosal blood flow and protection against potentially noxious agents. Gastric mucosa of ulcer patients tends to generate smaller amounts of PGs of E and I series and exhibits a reduced ratio of PG to thromboxane generation, which suggests that the deficiency of protective PG may play a role in the pathogenesis of peptic ulcer. Suppression of mucosal generation of PGs by non-steroidal anti-inflammatory compounds causes mucosal damage and increases the risk of the formation or exacerbation of peptic ulcer. Exogenous PGE and its stable analogs have been tested successfully in the treatment of GU and DU and the results so far obtained indicate that these agents significantly increase the ulcer healing rate. Certain anti-ulcer drugs such as carbenoxolone, sucralfate, colloidal bismuth and cimetidine appear to exert their beneficial effects on ulcer healing by mediating the release of endogenous PGs.     

Mucosal coating agents and other nonantisecretory agents

Gastric cytoprotection is protection against gross and histological gastric mucosal injury by a mechanism other than inhibition of neutralization of gastric acid secretion. Animal studies have shown that a variety of agents afford such a protective effect. With some of these agents, a similar protective effect has been shown in man. This protective effect must be distinguished from an action that enhances healing of an already established mucosal lesion as an ulcer. It is yet to be established that the cytoprotective effect of an agent enhances ulcer healing. Agents other than prostaglandins that have been shown to possess such a cytoprotective effect in animals are reviewed. Some, such as sucralfate, act via stimulation of endogenous prostaglandin synthesis, while others, such as DeNol, neomycin, and meciadanol, do not. Investigation of the mechanism through which these agents enhance gastric mucosal defense is a fertile field for investigation.This work was supported by VA medical research funds.Presented at the Annual Postgraduate Course of the American Gastroenterological Association, San Francisco, California, May 18, 1986.     

Comparative mucosal protective properties of misoprostol,cimetidine, and sucralfate

Misoprostol, a PGE₁ derivative that inhibits gastric acid secretion in rats, was compared with cimetidine and sucralfate in several rat experimental ulcer models. Gastric lesions were produced by aspirin, indomethacin, stress, sodium taurocholate, and ethanol. In all tests, misoprostol (50, 100, and 200 μg/kg) and cimetidine and sucralfate (50, 100, and 200 mg/kg) were administered intragastrically. Misoprostol protected against gastric lesions in all five experimental ulcer models at lower than gastric antisecretory doses. Cimetidine protected in the indomethacin, aspirin, and stress models, but only at gastric antisecretory doses, and did not protect against lesion formation in the ethanol and taurocholate models. Sucralfate, over the dose range tested, was not consistently protective in any of the five experimental ulcer models. It is concluded that misoprostol provides gastric mucosal protection against a wide variety of noxious agents by means of a unique mechanism and that reduction of gastric acid secretion is not required, as it is with cimetidine, for the protective effect.     

芩连合剂拮抗幽门螺杆菌延缓胃溃疡愈合作用及机制研究

[目的]探讨芩连合剂对幽门螺杆菌(Hp)延缓乙酸性胃溃疡愈合的治疗作用及其机制.[方法]在乙酸诱导大鼠实验性胃溃疡模型的基础上,感染NCTC11637株Hp,造成慢性胃溃疡模型,运用原位杂交等技术观察芩连合剂对Hp感染的慢性胃溃疡大鼠碱性成纤维生长因子(bFGF)mRNA、诱生型一氧化氮合成酶(iNOS)mR-NA等指标的影响.[结果]Hp加乙酸组和乙酸组均出现明显溃疡,芩连合剂高、中、低剂量组与Hp加乙酸组相比溃疡底部及周围胞质中bFGF mRNA表达均明显增强、iNOS mRNA均表达减少.[结论]芩连合剂能有效拮抗NCTC 11637株Hp对慢性胃溃疡的延缓愈合,其作用机制与该方促进溃疡周围bFGF合成增加,抑制iNOS活性等有关.     

Treatment of the gastric stump ulcer: an open study with five drugs

BACKGROUND/AIMS: Despite a great progress in the treatment of peptic ulcer disease, the management of gastric stump ulcers still remains to be established. METHODOLOGY: Eighty-one patients with peptic ulcer developed postoperatively in the gastric remnant were treated in an open trial with 5 antiulcer drugs (cimetidine, omeprazole, sucralfate, colloidal bismuth and misoprostol) characterized by different mechanisms of action. The ulcer healing rate was evaluated endoscopically after 2, 4 and 6 weeks. RESULTS: It was found that after 2 weeks the most rapid ulcer healing was in the omeprazole and cimetidine treated groups, 67 and 43% of healing, respectively. Also after 4 weeks the antisecretors were more effective than gastroprotective drugs; ulcer healing rate for omeprazole was 87% and cimetidine 68%, while for sucralfate, colloidal bismuth and misoprostol 50%, 52%, and 33%, respectively. After 6 weeks all drugs represented very close ulcer healing rates. CONCLUSIONS: Both antisecretory and gastroprotective drugs may be useful in the management of stump ulcers, however, to initiate and accelerate the stump ulcer healing omeprazole appears to be the drug of choice.     

Gastrocytoprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins.

This study compares the gastroprotective effects of colloidal bismuth subcitrate (De-Nol) with those of sucralfate and a methylated analogue of prostaglandin E2 (PGE2) against acute gastric lesions induced by acidified aspirin and absolute ethanol in rats. Both De-Nol and sucralfate given orally prevented dose dependently the formation of gastric lesions by these ulcerogens, De-Nol being, respectively, twice and seven times more potent, on a weight basis, than sucralfate. As the gastroprotective activities of both De-Nol and sucralfate on ethanol lesions can be reversed by pretreatment with indomethacin and as De-Nol and sucralfate increase the mucosal generation and luminal release of PGE2, we postulate that mucosal prostaglandins may be involved in the mechanism of action of these drugs on the gastric mucosa.     

Gastric protection by sucralfate. Role of mucus and prostaglandins

Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg X day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0-5, and to obtain biopsy specimens for determination of mucosal prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha. Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.