Vit D受体/CAMP通路在Vit D3体内抗幽门螺杆菌中的作用及机制研究

Helicobacter pylori can cause gastric cancer and other digestive diseases, but the eradication treatment failure due to drug resistance baffled physicians. Our previous research showed that vitamin D had the effect of anti Hp in vitro and in vivo, and cathelicidin antimicrobial peptide (CAMP) could offset Hp induced chronic gastritis in mice. Therefore we proposed a hypothesis, Vit D anti Hp effect in vivo was related with the pathway Vit D receptor (VDR) /CAMP. Hp strain and Vit D3 were planned to use as intervention, mice as the research object, to explore the expression VDR, CAMP and proinflammatory cytokines in mouse gastric mucosa after Hp infection; the effect on Hp colonization, gastric mucosal histopathology and CAMP expression after VDR gene knockdown; the effect of 1,25 (OH)2D3 on Hp colonization, gastric mucosal histopathology as well as VDR, CAMP and cytokines expression after Hp infection. The research will provide a new strategy for Hp eradication.

幽门螺杆菌（Hp）可引起胃癌和其他消化系统疾病，但其药物耐药性越来越成为困扰治疗的难题。我们前期工作发现，维生素D在体内外都具有抗Hp作用，并且抑菌肽（CAMP）在Hp诱发小鼠慢性胃炎中发挥重要作用。因此我们提出假说，体内Vit D抗Hp作用与VitD受体（VDR）/CAMP有关。我们拟以Hp和Vit D3为处理和干预手段，以小鼠为研究对象， 探讨Hp感染后小鼠胃粘膜VDR、CAMP 和细胞因子表达的变化；VDR基因敲低小鼠Hp感染后对胃粘膜Hp定植、病理组织学以及CAMP表达的影响；1,25(OH)2D3干预对Hp感染小鼠胃粘膜病理组织学以及VDR、CAMP 和细胞因子表达影响。研究结果将对Hp根除策略提供新的思路。

幽门螺杆菌（Hp）感染与胃癌的发生和发展密切相关，故认为消除Hp感染应有助于预防胃癌。有相关的临床研究观察到维生素D（VitD，1,25（OH）2D3）具有抗菌活性，但其抗Hp感染的作用效果结论不一致，且其潜在机制不明。在这项研究中，我们在野生型和VDR敲低（VDR-KD）小鼠中建立了小鼠Hp感染模型，并用于证明VitD通过增强VitD受体（VDR）和cathelicidin和VDR的表达抑制Hp感染，且VDR表达较低的VDR-KD鼠对Hp感染的敏感性更高。在培养的小鼠原代胃上皮细胞中，我们通过荧光素报告酶基因法进一步证明VitD / VDR复合物与cathelicidin启动子区域结合以增加其表达，这些结果在小鼠分子水平上提供了VitD抗Hp感染活性的机制解释。这项研究为Hp根除疗法的临床治疗提供了新途径，尤其是在针对于产生抗生素耐药性的Hp根除治疗。