miR-361-5p等miRNA对鸟分枝杆菌复合群疾病的早期诊断和在感染中的作用机制研究

鸟分枝杆菌复合群（Mycobacterium avium complex, MAC）在非结核分枝杆菌中占重要地位，引起的MAC疾病的临床表现与结核分枝杆菌复合群感染类似，实现MAC疾病的早期诊断和精准分型有助于MAC肺病的合理治疗，也有利于耐药肺结核的治疗和控制。现有诊断方法不能满足MAC疾病早期精确诊断的目的。因此，本研究拟采用全基因组测序对MAC进行分子分型，并建立MAC疾病的精准分型；建立RT-qPCR法在临床样本中验证及前瞻性评估前期研究中筛选到的MAC感染相关miRNA，明确miRNA对MAC疾病和不同型别MAC疾病的诊断能力；此外，运用细胞感染模型，探究具有诊断意义的miRNA（如miR-361-5p）在MAC感染中的作用及机制，明确其靶向调控的信号通路，不仅为miRNA作为MAC疾病的标志物提供理论基础，也为MAC疾病的预防和治疗提供科学依据。

Mycobacterium avium complex (MAC) was the most important pathogen in non-tuberculous mycobacteria, caused infections which shared common clinical features with diseases caused by mycobacterium tuberculosis complex. Therefore, early diagnosis and accurate typing of MAC diseases were significant not only for the therapy of MAC diseases, buy also the control of drug resistant-tuberculosis. However, the examination methods used currently could not distinguish MAC diseases from other mycobacterial infections in the early phase of diagnosis. Therefore, the MAC diseases were typed based on the genotypes of MAC strains generated by whole genome sequencing. The associations between the genotypes of strains and clinical features of MAC diseases were established. Then, the candidate serum miRNAs (e. g: miR-361-5p), which showed a potential significance in diagnosis of MAC diseases, were validated by RT-qPCR in this study and further were used to relate with the types of MAC diseases. At last, the functions of miR-361-5p were explored in the MAC infection model, to investigate how it regulated the lives of intracellular MAC. This study would contribute to the accurate diagnosis of MAC disease and clarify the mechanism of how the miRNAs functioned in MAC infection, providing new potential targets for immunotherapy for MAC disease in the future.