幽门螺杆菌在Barrett食管发病中的作用

The pathogenesis of precancerous disease, Barrett's esophagus, is still unclear. At present, it is still controversial over the inhibiting or provoking effect that helicobacter pylori (H.pylori) has on Barrett's esophagus. The latest study revealed that H.pylori has the ability to colonize in sites of esophageal mucosal inflammation, ulceration as well as columnar-lined epithelium metaplasia, which further accelerates the process of inflammation, ulceration and metaplasia. What's more, in the past studies, we have already demonstrated that H.pylori can colonize in esophageal mucosa and exacerbate esophageal inflammation in our surgical rat model of gastroesophageal reflux. However, limitations for the sake of surgical Barrett's esophagus animal model are obvious. So, based on the Barrett's esophagus mouse model of zinc deficiency and deoxycholic acid supplement, we performed this study in which we infected mouse model separately with H.pylori SS1 wild strain and cagA mutate strain by oral-gastric pathway, and made qualitative, quantitative and localizing detection of H.pylori by pathology, and analyzed esophageal inflammation, oxidative injury, squamous epithelium and columnar epithelium transcription factor and differentiation factor etc. from mRNA and protein levels, to demonstrate the effect H.pylori, especially cagA , has on the pathogenesis of Barrett's esophagus. Our study set a foundation for the treatment and prevention of Barrett's esophagus and esophageal adenocarcinoma.

癌前病变Barrett食管(BE)的发病机制不完全清楚，H.pylori对BE的发病有抑制或促进作用，目前仍有争议。最新研究发现，H.pylori可以在食管黏膜炎症、溃疡及柱状上皮化生部位定植，可能促进食管黏膜炎症和肠上皮化生。我们既往的研究证实，在大鼠反流手术模型中，H.pylori可在食管定植，并加重食管黏膜炎症程度。由于手术BE模型的诸多局限性，本研究以缺锌+脱氧胆酸处理的BE小鼠模型为基础，经口胃途径感染H.pylori SS1野生株及cagA突变株，通过病理观察及分子生物学实验，对H.pylori进行定性、定量及定位检测，分别从mRNA及蛋白水平检测食管炎症、氧化损伤、鳞状上皮及柱状上皮转录和分化因子等指标，论证H.pylori食管定植在BE发病中的作用和机制，特别是cagA基因在BE发病中的作用。本研究将为治疗BE，预防食管腺癌奠定基础。

Barrett食管为食管鳞状上皮发生柱状上皮化生,并有含杯状细胞的特殊肠上皮化生,是食管腺癌的癌前病变。目前尚无相对理想的Barrett食管的动物模型。本研究予以C57BL/6小鼠缺锌饮食未能诱导食管黏膜出现柱状上皮化生。缺锌饮食使小鼠进食量减少，体重减轻，补充锌后小鼠进食量及体重明显改善。缺锌组小鼠食管黏膜组织及血清锌含量降低，补充锌饮食可以改善，但食管黏膜组织锌含量增加程度低于血清锌。缺锌饮食使食管黏膜基底细胞增生，排列紊乱，食管角质层增厚，PCNA、P38、NFkB p105、NFkB p65、COX2表达显著增加，补充锌2周后，食管黏膜PCNA、NFkB p105、COX2表达减少，NFkB p65、P38表达无明显变化。缺锌饮食增加食管黏膜组织炎症因子表达，与缺锌组相比，补充锌2周后可以显著降低食管黏膜炎症因子S100A8、S100A9、NFkB表达，而HIF1α无明显变化，Saa3表达增加。