sRNA调控毒力蛋白在幽门螺杆菌所致胃黏膜损伤及替硝唑治疗中的作用机制

Helicobacter pylori (Hp) infection is an important cause of chronic gastritis and peptic ulcer, which has high recurrence rate and drug resistance. However, the mechanism of pathogenesis of Hp is unclear. Bacteria small non-coding RNA (sRNAs), 50~500nt nucleotides in length, is a kind of widespread RNA in prokaryotic organism and plays vital roles in the colonization, virulence and sensitivity to drugs of bacteria. Our preliminary experiments show that sRNA020/OipA may involve in Hp-induced gastric mucosa epithelial cell inflammation and reduced cystine/glutamate transporter. Tinidazole (TNZ) is used for Hp treatment and its exact mechanism has not been fully understood. Our early experiments also show that Hp sRNAs expression has been changed significantly accompanying with bacterial death after treat with TNZ. All this results indicate that Hp sRNA may mediate Hp-induced gastric injury and antimicrobial sterilization. This project intends to build Hp sRNA database, revealing the combining sequence and possible function of sRNA by bioinformatics analysis. On this base, we aim to test the important role of sRNA020/OipA in Hp-induced gastric injury in vivo and vitro and explore the role of sRNA in Hp therapy with TNZ. This project will study the function of bacteria sRNA as a novel pathogenic factor and therapy target from a new sight, which will help to reveal a new pathogenic mechanism and antimicrobial therapy for bacteria.

幽门螺杆菌（Hp）诱发溃疡的病理生理机制十分复杂。新近研究表明存在于Hp中的sRNA影响细菌定植、致病和药物敏感性，提示某些sRNA可能在诱发胃黏膜损伤和抗菌药物治疗中均起重要作用，但具体机制不明。我们前期通过深度测序获得Hp sRNA表达谱，并基于生物信息学分析及预实验发现：sRNA020靶向调控毒力蛋白OipA，降调sRNA020可降低OipA表达，减轻胃黏膜细胞损伤；抗菌药物替硝唑抑制Hp生长同时影响sRNA表达。故我们推测sRNA可能通过靶向毒力蛋白而介导Hp致胃粘膜损伤和替硝唑抗菌治疗过程。本项目拟基于sRNA表达谱，通过生物信息学和实验发现参与Hp致病及替硝唑抗菌治疗的候选sRNA，并经抑制与过表达分析确证其靶蛋白；在此基础上，通过细胞和在体动物确证sRNA调控胃黏膜损伤的机制。本研究拟从细菌致病和抗菌药物治疗两个角度，揭示sRNA可能是一种新的细菌致病物质基础和治疗靶标。

幽门螺杆菌（Hp）诱发溃疡的病理生理机制十分复杂。新近研究表明存在于Hp中的sRNA影响细菌定植、致病和药物敏感性，提示某些sRNA可能在诱发胃黏膜损伤和抗菌药物治疗中均起重要作用，但具体机制不明。我们前期通过深度测序获得Hp sRNA表达谱，并基于生物信息学分析及实验发现：sRNA020靶向调控毒力蛋OipA，下调sRNA020可降低OipA表达，减轻胃黏膜细胞损伤；抗菌药物替硝唑抑制Hp生长同时影响sRNA表达。我们研究发现sRNA可能通过靶向毒力蛋白而介导Hp致胃粘膜损伤和替硝唑抗菌治疗过程。本项目基于sRNA表达谱，通过生物信息学和实验发现参与Hp致病及替硝唑抗菌治疗的候选sRNA，并经抑制与过表达分析确证其靶蛋白；在此基础上，通过细胞和在体动物确证了sRNA调控胃黏膜损伤的机制。本研究从细菌致病和抗菌药物治疗两个角度，揭示sRNA可能是一种新的细菌致病物质基础和治疗靶标。