透明质酸铋的抗幽门螺杆菌及促溃疡愈合活性研究01.doc

透明质酸铋的抗幽门螺杆菌及促溃疡愈合活性研究 凌沛学, 金艳（山东省生物药物研究院Bi3+-hyaluronate complex，BiHA）的抗幽门螺杆菌（H. pylori）活性和对大鼠实验性慢性胃溃疡愈合的影响。方法 采用琼脂稀释法检测BiHA对H. pylori的最低抑菌浓度（MIC）。观察BiHA对醋酸致大鼠慢性胃溃疡愈合的影响。采用ELISA检测大鼠胃部黏膜中的NO含量和表皮生长因子（EGF）表达量，初步探讨BiHA的作用机制。结果 BiHA具有与枸橼酸铋钾相近的体外抗菌活性。BiHA能够促进慢性胃溃疡的愈合，且能提高溃疡愈合质量。BiHA促进慢性胃溃疡愈合的作用机制可能与其增加胃黏膜中EGF的表达有关。结论 BiHA具有良好的抗H. pylori；溃疡；愈合 Anti-H. pylori and Ulcer-healing Activity of a Bi3+-hyaluronate Complex LING Pei-xue, JIN Yan (Institute of Biopharmaceuticals of Shandong Province, Jinan 250101, China) ABSTRACT: OBJECTIVE To investigate the anti-H. pylori activity and effect on the healing of experimental chronic ulcer in rats of a Bi3+-hyaluronate complex (BiHA). METHODS The MICs of BiHA against H. pylori were tested by agar dilution method. Effect of BiHA on healing of chronic gastric ulcer in rats induced with acetic acid was also evaluated. The NO contents and expression of EGF in gastric mucosa of rats were tested by ELISA to explore the action mechanism of BiHA. RESULTS BiHA showed similar anti-H. pylori activity to that of bismuth potassium citrate. BiHA could accelerate the healing of chronic ulcer and increase the quality of ulcer healing. The increase of EGF expression in the gastric mucosa may be one of the ulcer-healing mechanisms of BiHA. CONCLUSION BiHA possesses favorable anti-H. pylori and anti-ulcerogenic activity and may be developed into a drug exploited in therapy of peptic ulcer disease. KEY WORDS: Bi3+-hyaluronate complex; H. pylori; ulcer; healing 消化性溃疡疾病是一种慢性消化系统疾病，发病率较高。研究表明，消化性溃疡的发病主要是胃肠道黏膜的侵袭因素和保护因素失衡所致。幽门螺杆菌（H. pylori）H. pylori活性和黏膜保护活性，因而在消化性溃疡的治疗中获得广泛应用。透明质酸（HA）是一种由N-乙酰氨基葡糖和葡糖醛酸双糖重复单位形成的糖胺聚糖，具有多种生物活性，如构成多种基质、保水及润滑、创伤愈合等[1]。HA及其衍生物在医药领域获得广泛应用。HA的金属配合物近年来也受到人们的重视。本文对HA与Bi3+形成的配合物透明质酸铋的抗H. pylori活性及促溃疡愈合作用进行了研究。 1 材料和方法 1.1 仪器与材料 超净工作台（济南洁康空气净化设备厂）；生化培养箱（北京市永光明医疗仪器厂）；T8.01 Netzger?t型电动匀浆器（德国IKA?-WERKE）；Multiskan Mk 3酶标仪（芬兰Thermo Labsystems）。 透明质酸铋（BiHA，自制，铋含量为25.60％150~200 g，♀♂兼用（山东大学新药评价中心）。 1.2 方法 1.2.1 BiHA的体外抗H. pylori