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目的:研究质子泵抑制剂(PPI)处理不同时间大鼠空肠细菌菌群结构和组成的改变,探讨抑制胃酸与肠道感染发生之间的潜在联系。方法:以大鼠为实验动物,对照组不给药(0 d),实验组连续腹腔注射奥美拉唑第5、9、14、21和28天,每天2次,每次10 mg/kg。研究结束次日处死动物,收集空肠内容物,提取DNA,PCR扩增16S rRNA基因V3区,行变性梯度凝胶电泳(DGGE),切胶测序确定细菌种属,并分析其相对丰度变化。结果:与正常对照比,短期PPI处理(第5和9天)菌群变化相对较小,菌群相似度分别为(74.8±3.0)%和(70.9±7.5)%,肺炎链球菌(Streptococcus pneumoniae)、化糖梭状芽胞杆菌(Clostridium saccharolyticum)和格氏乳球菌(Lactococcus garvieae)相对丰度增加,共生菌罗伊乳杆菌(Lactobacillus reuteri)和柯林魏斯菌(Weissella koreensis)明显减少。随着给药时间延长,菌群变化程度加剧。第14天后,条件致病菌粪肠球菌(Enterococcus faecalis)过度增长,并取代罗伊乳杆菌成为最优势细菌。第21天致病菌难辨梭状芽胞杆菌(Clostridium difficile)在大鼠空肠出现和定植;至第28天菌群组成变化最大,与0 d比相似度仅约(56.1±16.7)%。结论:短期给予PPI处理可诱导大鼠空肠菌群改变,但变化较小。长期胃酸抑制(>14 d)可导致空肠菌群失衡,致病菌丰度增加,可能为肠道细菌感染形成的关键诱因。
Objective: To study the change of structure and composition of jejunal bacteria in proton pump inhibitor (PPI) -treated rats at different time and to explore the potential relationship between inhibition of gastric acid and intestinal infection. Methods: The rats were used as experimental animals and the control group was given no drug (0 d). In the experimental group, omeprazole was injected intraperitoneally on the 5th, 9th, 14th, 21st and 28th day of the experiment, twice a day for 10 mg / kg . The animals were sacrificed on the following day. The contents of jejunum were collected and DNA was extracted. The V3 region of 16S rRNA gene was amplified by PCR. Denaturing gradient gel electrophoresis (DGGE) was carried out. The bacterial species were determined by gel electrophoresis and the relative abundance was analyzed. Results: Compared with the normal control, the changes of bacterial population in short-term PPI treatment (days 5 and 9) were relatively small with the similarity of (74.8 ± 3.0)% and (70.9 ± 7.5)%, respectively. Streptococcus pneumoniae ), The relative abundance of Clostridium saccharolyticum and Lactococcus garvieae increased, and the symbiotic bacteria Lactobacillus reuteri and Weissella koreensis significantly decreased. As the dosing time prolonged, the degree of flora increased. After 14 days, the pathogen Enterococcus faecalis overproduced and replaced L. reuteri to become the most dominant bacterium. The pathogen Clostridium difficile appeared and colonized in the rat jejunum on the 21st day. The composition of the flora changed the most on the 28th day, with only about 56.1 ± 16.7% similarity to the 0 day. Conclusion: The short-term administration of PPI can induce the change of jejunal flora in rats, but the change is small. Long-term gastric acid suppression (> 14 d) can lead to imbalance of the number of jejunal bacteria, increased pathogenic bacteria, may be the key cause of intestinal bacterial infection.