【作者】 韦家勇；

【导师】 柳忠辉； 余秋颖；

【作者基本信息】 吉林大学 ， 免疫学， 2008， 硕士

【摘要】 消化性溃疡(peptic ulcer, PU)是一种胃肠道黏膜及黏膜肌层坏死性病理损伤过程,其愈合需要上皮组织和结缔组织的重建。生长因子通过促进细胞增殖和迁移、血管生成及结缔组织再生,在溃疡愈合过程中发挥着重要作用,已经成为抗消化性溃疡药物作用的新靶点。本研究通过制备乙酸烧灼型胃溃疡大鼠模型,观察新合成的抗溃疡药物——正丁胺基罗沙替丁乙酸酯(Butylamine roxatidine derivate,BRD)对乙酸烧灼型胃溃疡大鼠胃黏膜表皮生长因子(epidermal growth factor,EGF)及其受体(epidermal growth factor receptor,EGFR)表达的影响,探讨正丁胺基罗沙替丁乙酸酯促进消化性溃疡愈合的作用机制。实验结果显示,胃溃疡模型大鼠胃黏膜毛细血管扩张、充血,灶性出血明显,间质可见大量的炎性细胞浸润,部分区域黏膜坏死、脱落,局部腺体有破坏。阳性对照药雷尼替丁组、正丁胺基罗沙替丁乙酸酯高剂量和中剂量组的黏膜溃疡均可见不同程度的愈合,溃疡灶表面有新生上皮覆盖,炎性细胞明显减少,可见新生的腺体覆盖溃疡和增生的纤维结缔组织,溃疡底部有明显肉芽组织形成,正丁胺基罗沙替丁乙酸酯低剂量组溃疡愈合不明显。免疫组织化学染色显示对照组EGF及EGFR表达为弱阳性,各剂量组的表达有明显差异。正丁胺基罗沙替丁高、中剂量组及阳性药物雷尼替丁组EGF及EGFR表达明显增高,正丁胺罗沙替丁小剂量组EGF及EGFR表达升高不明显。上述资料提示正丁胺基罗沙替丁乙酸酯促进溃疡愈合作用与其上调EGF及EGFR表达有关。更多还原

【Abstract】 Peptic ulcer (peptic ulcer, PU) is a gastrointestinal mucosa and submucosa muscle necrosis pathological injury, the need for healing epithelial tissue and connective tissue reconstruction. H2 receptor antagonists selectively binding on the membrane wall of the H2 receptor, the cell wall of cAMP generated, reduce gastric acid secretion. H2 receptor antagonist not only to histamine-stimulated acid secretion is inhibited, but also partially inhibited gastrin and acetylcholine-stimulated acid secretion, and promote mucosal ulcer healing. EGF is a 53 amino acid composition of the single-chain polypeptide,Mainly come from the submandibular gland, duodenum Brunner gland, renal tubular cells, pancreas, thyroid and liver, etc,In the gastric mucosa can also detect low levels of EGF protein. Through its specific EGF receptor (EGFR) combined to play in maintaining its integrity and mucosal injury and repair in the process of important biological role.Objective:Through the observation of the new H2-receptor antagonist-the effects of butylamine roxatidine derivate(BRD) on expresstions of EGF and EGFR in rat with gastric ulcer,discussion is BRD acetate for the promotion of peptic ulcer healing mechanism.Methods:48 from Wistar rats were randomly divided into six groups, each with eight, namely: (1) control group, to appropriate saline gavage (2) ulcer model control group, to appropriate saline gavage (3) to (5) butylamine roxatidine derivate(BRD) high for the small acetate, , the low-dose group (28 mg / kg, 14mg/kg, 7mg/kg) (6) drug Ranitidine positive control group (27 mg / kg). (2) to (6) rats using acetic acid burning Preparation gastric ulcer model, not the normal control group rats surgery.Rats after 15 days of continuous intragastric administration in the last administration after fasting for 24 hours, free drinking water, the first 16 days will be broken cervical rats were sacrificed, drawing. HE staining of butylamine roxatidine derivate(BRD) for small acetate rat mucosa of the gastric ulcer healing the impact of immunohistochemical staining of gastric EGF and EGFR expression.Results:1. HE staining of the rats ulcer formation and healing: Normal control group: the rat gastric antral wall structural ntegrity, glandular mucosa neat, and there was no obvious inflammatory cell infiltration.Model group: Gastric telangiectasia, congestive, focal bleeding obvious that a large number of interstitial infiltration of inflammatory cells, and some regional mucosal necrosis, exfoliated, local glands damaged.Treatment group: ranitidine, butylamine roxatidine derivate(BRD) small acetate for high-dose and the dose of mucosal ulceration were observed varying degrees of healing ulcer lesions have varying degrees of the surface epithelium new coverage, inflammatory cells decreased significantly, we can see that the nascent gland hyperplasia coverage ulcers and fibrous connective tissue, obviously at the bottom of ulcer formation of granulation tissue, vascular mild gastric expansion, congestive.2. Renewable rat gastric mucosal thickness, the muscularis mucosa defects of the results of comparison:Renewable thickness of the gastric mucosa statistical analysis shows that for butylamine roxatidine derivate(BRD) acetate in small doses and high dose group, ranitidine group and the untreated group model has obvious significant difference, p <0.01 .Comparing the muscularis mucosa defects of the statistical analysis showed that butylamine roxatidine derivate(BRD) small acetate for the high dose group, ranitidine group and group therapy model has obvious significant difference, p <0.01.3.Experimental gastric ulcer rat mucosa EGF and EGFR immunohistochemical staining:Immunohistochemical staining showed that the normal control group EGF and EGFR expression was weakly positive for small butylamine roxatidine derivate(BRD) high dose group and the positive drug Ranitidine group EGF and EGFR expression was significantly increased. butylamine roxatidine derivate(BRD) for the small-dose group increased expression of EGF and EGFR not obvious. These data suggest that n-butylamine Jiluosha acetate for the treatment of small ulcer in the process, for the dose-dependent expression of EGF and EGFR, EGF and EGFR may be mediated by di-n-butylamine Jiluosha for small acetate promote ulcer healing role.Conclusion:The successful establishment of the rat gastric ulcer model. butylamine roxatidine derivate(BRD) study found that for a small increase in acetate ulcer mucosal lesions and the surrounding renewable thickness, width decreased muscularis mucosa defects, and promote epithelial tissue regeneration capabilities, and improved weary scar repair, butylamine roxatidine derivate(BRD) study found that for a small increase in acetate ulcer mucosal lesions and the surrounding renewable thickness, width decreased muscularis mucosa defects, and promote epithelial tissue regeneration capabilities, and improved weary scar repair, Granulation tissue, there by stimulating the formation of microvascular, inhibit secretion of parietal cells, and stimulate the ulcer edge epithelial cell proliferation, differentiation, migration and increased mucosal blood flow, and enhance the mucosal regeneration glands function, and promote ulcer healing.更多还原