长期应用质子泵抑制剂对幽门螺杆菌感染小鼠的影响及机制初探
本文选题:幽门螺杆菌 + 质子泵抑制剂 ; 参考:《南京医科大学》2014年硕士论文
【摘要】:背景:幽门螺杆菌(Helicobacter pylori, H. pylori, Hp)感染是导致胃炎、消化性溃疡和胃癌的的主要病原菌。质子泵抑制剂(proton pump inhibitors,PPI)是有效的胃酸分泌抑制剂,是治疗消化性溃疡、上消化道出血等酸相关疾病的主要药物。但近年来,长期PPI治疗的安全性越来越受到质疑。有研究显示长期服用PPI可以引起微量营养物质吸收障碍、增加肠道感染发生率,在Hp阳性个体甚至促进胃底腺息肉、萎缩性胃炎等癌前病变的发生,但最终结论仍然有争议。目的:研究长期服用PPI对Hp感染的C57BL/6小鼠的影响,主要观察其对胃粘膜的影响以及胃癌相关基因的改变。方法:60只C57BL/6小鼠随机分为A、B、C、D四组,每组15只。A组为空白组,B组为Hp组,C组为PPI组,D组为Hp+P PI组。其中C和D组予含有0.05%埃索美拉唑的饲料喂养。饲养45周后,每组处死5只,57周时处死每组剩下的10只。小鼠处死后测定胃湿重和胃内pH,并将胃粘膜进行HE染色和Giemsa染色,分别观察胃粘膜病理情况和Hp感染情况。用ELISA法测定小鼠血浆胃泌素和TFF1的水平,real-time PCR检测小鼠胃黏膜IL-6、SOX2、CDX2、MUC5AC和TFF1基因的表达。结果:服用含有PPI饲料的C组和D组胃内pH较A、B组明显升高,胃湿重也均较A、B组重。A、B、C和D在45周和57周处死时,均无肠上皮化生、萎缩性胃炎等癌前病变,A和C组胃粘膜正常,B组可见急慢性炎症表现,D组亦可见急慢性炎症,但炎症程度比B组重(P=0.000)。D组血浆胃泌素水平在45周和57周均最高。胃粘膜IL-6水平在B和D组均较A组升高,且57周时D组比B组明显升高。胃粘膜SOX2的表达在B组轻度降低,在D组进一步下降,而CDX2在B组上升,在D组进一步上升。胃粘膜TFF1的水平和血浆TFF1水平表达不一致。结论:1、成功建立长期服用PPI伴Hp感染的C57BL/6小鼠模型。2、C57BL/6小鼠感染Hp14个月后可导致胃粘膜炎症,并未产生萎缩性胃炎、肠上皮化生及不典型增生等癌前病变。3、PPI与Hp协同作用,使C57BL/6小鼠血浆胃泌素水平升高。4、PPI可以加重Hp诱导的炎症反应,且呈现时间依赖性。5、Hp感染并应用PPI后,C57BL/6小鼠胃粘膜相关抑癌基因表达降低,促癌基因表达上升。
[Abstract]:Background: Helicobacter pylori (HP) infection is a major cause of gastritis, peptic ulcer and gastric cancer. Proton pump inhibitor (proton pump inhibitors) is an effective inhibitor of gastric acid secretion, and is the main drug for the treatment of peptic ulcer, upper gastrointestinal bleeding and other acid-related diseases. However, in recent years, the safety of long-term PPI treatment is increasingly questioned. Some studies have shown that long-term use of PPI can cause micronutrient absorption disorders, increase the incidence of intestinal infection in HP positive individuals and even promote the occurrence of precancerous lesions such as fundus polyps and atrophic gastritis, but the final conclusion is still controversial. Aim: to study the effect of long-term PPI on Hp-infected C57BL / 6 mice, and to observe the effect of PPI on gastric mucosa and the changes of gastric cancer related genes. Methods Sixty C57BL / 6 mice were randomly divided into four groups: group A (n = 15), group B (n = 15), group C (HP), group C (P Pi), group D (P Pi). Groups C and D were fed with a diet containing 0.05% esomeprazole. After 45 weeks of feeding, 5 rats were killed in each group and the remaining 10 rats in each group were killed at 57 weeks. The gastric wet weight and intragastric pH were measured after the mice were killed. The gastric mucosa was stained with HE and Giemsa. The pathological changes of gastric mucosa and HP infection were observed. The levels of plasma gastrin and TFF1 in mice were determined by Elisa and real-time PCR was used to detect the expression of MUC5AC and TFF1 genes in mouse gastric mucosa. Results: the intragastric pH of group C and D fed with PPI diet was significantly higher than that of group A B, and the wet weight of stomach was also higher than that of group A, B, C and D at 45 and 57 weeks after death, there was no intestinal metaplasia. Acute and chronic inflammation was also seen in group D, but the degree of inflammation was higher in group D than that in group B (P < 0.05). Plasma gastrin levels in group D were higher than those in group B (n = 45) and group C (n = 57). The level of IL-6 in gastric mucosa in group B and D was higher than that in group A, and at 57 weeks, the level of IL-6 in group D was significantly higher than that in group B. The expression of SOX2 in gastric mucosa decreased slightly in group B and decreased further in group D, while CDX2 increased in group B and increased in group D. The expression of TFF1 in gastric mucosa was not consistent with that in plasma. ConclusionThe mouse model of long-term PPI with HP infection in C57BL / 6 mice was successfully established. The infection of Hp14 months in C57BL / 6 mice with PPI could lead to gastric mucosal inflammation, without atrophic gastritis, intestinal metaplasia, atypical hyperplasia and other precancerous lesions, such as PPI and HP. The increase of plasma gastrin level in C57BL / 6 mice. 4 PPI could aggravate the inflammation induced by HP, and the expression of tumor suppressor genes in gastric mucosa of C57BL / 6 mice was decreased and the expression of oncogene was increased after PPI application.
【学位授予单位】:南京医科大学
【学位级别】:硕士
【学位授予年份】:2014
【分类号】:R573
【相似文献】
相关期刊论文 前10条
1 王爱平;张清林;黄春倩;沈伽弟;于文梅;王治乔;;小鼠血浆某些生化指标的影响因素探讨[J];军事医学科学院院刊;1992年04期
2 杨敏;王广基;王素军;李晓天;徐宇平;曹国宪;叶文才;;液相色谱-质谱联用测定鼠血浆中的23-羟基白桦酸[J];中国药学杂志;2006年21期
3 杨小明;张秀丽;夏磊;刘方;李永金;;反相高效液相色谱法测定小鼠血浆中银杏酸浓度[J];药物分析杂志;2009年04期
4 吴南屏,赵忠良,高文华;氟对小鼠血浆唾液酸含量的影响[J];卫生毒理学杂志;1993年02期
5 ;共存生药对日本防己抑制小鼠血浆碱性磷酸酶活性的影响[J];国外医学(中医中药分册);1996年04期
6 甘发平;韩铮;栾连军;周长新;吴永江;;高效液相色谱法测定小鼠血浆和脑中的丹参酮ⅡA及药代动力学研究[J];分析化学;2008年12期
7 徐军,胡月娟,李仪奎,叶福媛,张红梅,俞缨;黄芪、当归及其不同配伍煎液和给药后小鼠血浆中铁、铜元素含量测定[J];中药药理与临床;1993年04期
8 刘荣敏,程佳,杨祖贻,裴瑾,万德光,胡荣;小鼠血浆中微量阿魏酸提取分离方法实验研究[J];北京中医药大学学报;2005年05期
9 王艳芝;郑甲信;史启君;王彩莲;邓意辉;毕殿洲;;反相高效液相色谱法测定小鼠血浆中β-榄香烯含量[J];郑州大学学报(医学版);2007年06期
10 缪解铃,王兆林,俞文峰,杨国栋;东莨菪碱对小鼠血浆睾酮和雌二醇含量的影响[J];中国药理学通报;1992年06期
相关会议论文 前5条
1 丁敏;小林裕太;福岛正充;;GC-MS测定小鼠血浆的尼古丁和可替宁[A];第十五次全国色谱学术报告会文集(上册)[C];2005年
2 陈丽红;陈晨;刘承伟;卢昕;;高效液相色谱串联紫外荧光同时检测小鼠血浆中的八羟基脱氧鸟苷和多巴胺[A];全国生物医药色谱及相关技术学术交流会(2012)会议手册[C];2012年
3 陈汀;姚卫峰;张丽;丁安伟;;基于UPLC-TOF-MS的CCl4诱导肝损伤小鼠血浆代谢组学研究[A];2010中药炮制技术、学术交流暨产业发展高峰论坛论文集[C];2010年
4 赵锐;宋宇;杨丽;;酸提水溶玉米芯硫酸酯化多糖对荷瘤小鼠血浆CuZn-SOD及MDA的影响[A];中国微量元素科学研究会第十三届学术研讨会论文集(二)[C];2006年
5 张成;王超;许宝山;夏国良;;3-羟-3-甲基戊二酰-CoA还原酶(HMGCR)基因调节小鼠血浆胆固醇代谢研究[A];全国动物生理生化第十次学术交流会论文摘要汇编[C];2008年
相关硕士学位论文 前4条
1 顾敏;长期应用质子泵抑制剂对幽门螺杆菌感染小鼠的影响及机制初探[D];南京医科大学;2014年
2 吴胜明;基于GC/TOF-MS小鼠血浆代谢组学技术方法的建立及其应用[D];中国人民解放军军事医学科学院;2010年
3 郭玲玲;电针对SAMP8小鼠血浆、肝肾组织~1H NMR谱图的影响[D];成都中医药大学;2008年
4 梅逸舟;芥子气全身中毒小鼠血浆蛋白质组和代谢组学的初步研究[D];中国人民解放军军事医学科学院;2011年
,本文编号:2031891
本文链接:https://www.wllwen.com/yixuelunwen/xiaohjib/2031891.html