广西巴马县幽门螺杆菌CagA相关的sRNA调控机制研究

幽门螺杆菌（Hp）是胃炎、胃癌等疾病的主要致病因子，世界卫生组织推荐根除Hp，但随着耐药率升高，根除率越来越低，迫切需要新的防治方案。我们研究发现长寿之乡广西巴马县人群的Hp菌株呈高度多态性，38.5%菌株细胞毒素相关蛋白A（CagA）阴性，阳性菌株大部分CagA表达量也低于悉尼株SS1等，而且发现CagA低表达与HP0165等非编码小RNA（sRNA）有关，这可能是该地区高感染、低发病的原因。但为什么低毒菌株这么多，sRNA与CagA如何调控，尚未清楚。因此，我们拟对巴马县各类型Hp菌株测序，预测sRNA；用qRT-PCR、报告基因等方法初步验证sRNA对CagA基因调控作用；用sRNA敲除、回补等实验确证；用敲除sRNA的巴马菌株等感染小鼠，观察胃病理损伤、菌株定植等，判断毒力变化，阐述广西巴马县Hp的sRNA调控CagA的作用机制，为研究减毒活疫苗、探索新的Hp防治方案提供依据。

Helicobacter pylori (Hp) is a major causative factor of gastritis and gastric cancer. The World Health Organization recommends Hp eradication , however, with drug resistance rate increasing, the rate of eradication is decreasing. New prevention and treatment methods are needed urgently. We have found that Hp strains are highly polymorphic in the population of Bama County, which is a township known for the longevity of its residents in Guangxi, 38.5 % of the strains are negative for cytotoxin-associated protein A (CagA), and most of the positive strains have lower CagA expression than the Sydney strain SS1. The low expression of CagA was related to some small non-coding RNA(sRNA), such as HP0165 , which may be the cause of high infection and low incidence in this area, however it is unclear why there are so many low-toxicity strains and how sRNA and CagA are regulated. Therefore, we plan to sequence Hp strains form Bama to predict sRNA; use qRT-PCR, Reporter gene, and other methods to verify the regulatory effect of sRNA on CagA gene. We attempt to confirm our findings with sRNA knockout and genetic complementation experiments. By infected mice with sRNA knockout Bama strains, then we observe the gastric pathological damage, strain colonisation, etc. and judge the virulence changes. The mechanism about Hp sRNA regulation of CagA will be elaborated in Bama County, Guangxi , which may provide a basis for studying live attenuated vaccines and exploring new Hp prevention and treatment schemes.