胃肠宁对溃疡愈合质量作用的实验与临床研究

【作者】 叶柳忠；

【导师】 许鑫梅；

【作者基本信息】 广州中医药大学 ， 中医内科学， 2000， 硕士

【摘要】 消化性溃疡（Peptic Ulcer）的复发是临床上较为棘手的问题，影响溃疡愈合与复发的因素有很多，包括幽门摞杆菌的感染。攻击因子失调的影响如：胃酸、药物及粘膜保护的减弱如：血液供应、细胞保护因子与生长因子的减弱等，而现代研究提出了溃疡愈合质量（QOUH）的概念，更指出了溃疡的复发与溃疡的愈合质量密切相关。溃疡愈合质量是包括了胃镜下粘膜成熟度，组织结构成熟度与功能成熟度三个方面的内容，全面的概括了溃疡愈合、成熟程度的评价标准。为中医药疗效的评价提供了全新的参照，中医学对PU的辨治多归于“胃脘痛”的范畴。祖国医学认为消化性溃疡发生及复发与六淫侵袭、情志失调、病邪阻络、正虚邪侵几个因素相关。现代对溃疡复发的认识多支持：脾胃虚弱为本，胃热郁火为标，血瘀阻络导致慢性迁延为患的观点。在PU的治疗中怎样提高溃疡的愈合质量是提高疗效、防止溃疡复发的关键。中药可以通过杀/抑HP，清热和胃，疏肝理气，活血化瘀，健脾益气等多个方面调整胃的内环境，促进溃疡愈合，并提高其愈合质量。观察并确证中药在提高QOUH上的疗效，正是本研究需要解决的问题。 本课题选用清热和胃，活血化瘀，生肌止痛的中成药胃肠宁为观察药物，雷尼替丁为对照药物，分动物实验和临床观察两部分，对溃疡愈合的组织学与胃镜形态学的成熟度进行观察：一.动物实验：采用慢性乙酸大鼠溃疡模型，在大鼠胃浆膜面诱导胃溃疡 并对治疗组，对照组与空白组分别予胃肠宁、雷尼替丁及生理盐水治 疗14天，并于次日处死各组半数大鼠取胃切片进行再生粘膜组织学 成熟度指标的检测，其余大鼠在经过一段适应期后再给予各组大剂量 强的松灌胃，诱导胃粘膜溃疡的再损伤。结果发现损伤前治疗组再生 粘膜宽度（P＜0.01）、粘膜肌层缺损宽度（P＜0.01）、厚度（P＜0.05）、 及囊状扩张腺体数（P＜0.05）均优于空白组，并在再生粘膜宽度上甚至 远远优于对照组（P＜0.01）。经诱导再损伤后，对照组与空白组的上述 指标均有了不同程度的恶化，而治疗组除粘膜肌层缺损宽度增宽外 O0．05X其余指标没有显著的改变仰川．05L甚至囊状扩张腺体更 明显减少Oo．ofh说明胃肠宁有效的起到了抗溃疡促愈合的作用， 并在改善溃疡再生癫痕的组织学成熟度方面优于雷尼替丁及生理盐 水，提高了再生粘膜抵御强的松再损伤的能力。二．临床观察；选取广州中医药大学第一附属医院门诊及内二科住院患者， 经胃镜发现属活动期消化性溃疡，并予中医辩证属肝郁胃热或肝胃不 和的病例。共纳入80例，随机分配到（胃肠宁＋雷尼替丁）治疗组50 例，（雷尼替丁）对照组 30例。分别给予胃肠宁 4片 t i d＋雷尼替丁 0．15 Bid，及单纯雷尼替丁0．15 Bid治疗，8周为一个疗程，单盲观察。并 于治疗前、经治第4周、治疗第8周，记录疼痛、腹胀、暧气、反酸、 便秘等症状的积分惰况；同时于治疗第8周与半年后复查胃镜，记录 S。期获得率与溃疡愈合率的情况。结果显示，胃肠宁＋雷尼替丁组对疼 痛、腹胀、暧气、反酸、便秘诸症均有显著的改善，而雷尼替丁组仅 对疼痛及反酸有效果。胃镜复查发现，治疗后第八周，治疗组溃疡愈合 率为82％，优于对照组的40％（P＜0．005），S；期获得率治疗组42W优于 对照组10叭P（．005L经治半年后，溃疡愈合率两组间差异不显著， 但S。期获得率治疗组86％仍明显优于对照组50％（P＜0．005），提示胃肠 宁结合雷尼替丁治疗消化性溃疡加速了溃疡愈合，并使溃疡愈合成熟 程度更趋于稳定。临床疗效证明胃肠宁不但有效地改善了M的临床 症状，还加速了溃疡愈合并提高了愈合质量。更多还原

【Abstract】 The recurrence of Peptic Ulcer (PU) is a thorny problem in clinic work. And the solution of this problem is increasing interest among clinical doctors and research workers. Many factors can affect peptic ulcexal healing and recurrence, incluing the constant HP infection , the uncontroled attacking factors like gastric acid, medical drugs , or the decrease in protection factors such as deterioration of blood supply, decline in cell-pretection agent and other growth factors. Current researches put forward a new concept of Quality Of Ulccral Healing (QOUH) , pointing Out the close relationship between ulceral recurrence and QOUH The concept of QOUH is composed of three parts of contents , namely morphological maturity degree of regenerating mucosa under endoscopy , histological maturity of regenerating mucosa, functional maturity degree of regeneraiing mucosa, which widely evaluates the maturity degree of Ulceral healing and consequently provides a new reference in the asessment of Chinese Medicine clinical result. The diagnosis and differentiation of Peptic Ulcer in Traditional Chinese Medicine is deiflned as tomach pain?(Wei Wan Tong). It is commonly acknoledged in TCM that the onset and relapse of peptic ulcer is associated with the attack of six climatic evils, disorder of emotions, meridian and collateral obstruction by excess as well as evil invasion due to deficiency And rnordon researchers more likely intend to accept the idea that this is a chronic and prolonged condition caused by primitive Spleen Qi deficiency and secondary stagnated stomach lIre along with blood stasis in channels In the IreaUnent of peptic ulcer, how to promote the QOUH has become a key point in improving results and preventing recurrence. As is known, Chinese Medicine plays an important part in killing and inhibiting HP, clearing heat and undistutting stomach, regulating liver qi , removing blood stasis ,and enforcing spleen qi It is likely to see Chinese Medicine can take great advantage over the adjustment of stomach抯 internal enviroment ,and the improvement of ulceral healing and promotion in healing quality To investigate and identify the act of Chinese Medicine on the above aspects is right the question we put in this research. in this research , a patent called ei Chang Niug~?(stomach and intestine calming ),possessing the nature of heat-clearing, stomach-calming and blood-moving ,aiong 3 with flesh-generating and pain-killing, is selected as observation drug in contmst to a control medicine of Ranitidine Animal experiment and clinical investigation were seperately undertaken to rate the histological and endoscopic morphological maturity degree. 1. Animal experiment A model of acetic acid chronic gastric ulcer on rat was obtained by inducing ulceration on the gastric serons coat of rats. A treatment was carried out after that surgery among treated group , control group and blank group , which were respectively fed with 揥ei Cluing Ning~? Ranitidine and normal saline.After 14 days of treatment, half number of rats in each group were killed by being taken stomach from, and the stomach samples were slided and measured on indicators of histological regenerating mucosa of maturity degree. The rest alive were all followed up by a large dorsage of predinisone treatment after an interval of regulation to induce redamage of the gastric ulcer. Results showed , before the redamage , regenerating mucosal width, mucosal muscular defect width and更多还原