耐药菌所致肺部感染是临床面临的棘手问题，耐药性的攀升和肺-血屏障导致药物分布困难使得增大剂量和联合应用抗菌药物都难以完全清除肺部感染且会带来不良反应增加的风险。低频超声(LFU)作为一种无创靶向物理治疗方法，在促药渗透和创面修复方面展示出独特的优势，并且课题组前期研究还发现LFU能加强抗菌药物对泛耐药细菌的抗菌活性。因此，基于LFU抗菌增效的研究结果，并考虑其可靶向作用于肺部加速系统性用药肺组织的分布可能性以及潜在的免疫调节和组织修复能力，我们首次提出“LFU联合抗菌药物治疗耐药菌所致肺部感染”的设想，设计分子、细胞和整体动物三个层面的系统实验，采用microarray方法全面解析调节修复的分子机制，构建活体动物成像肺部感染模型直观实时评价，从抗菌增效、促药分布和调节修复三方面深入研究LFU联合抗菌药物治疗耐药菌所致肺部感染的可行性和作用机制，为临床治疗难治性肺部感染提供新的思路和方法。

Pulmonary infection caused by multidrug resistant bacteria is difficult to treat in clinic. Increasing the dose and combination of antimicrobials can hardly completely remove the pathogen and will bring the higher risk of adverse reactions because of antimicrobial resistance and lung-blood barrier. Low-frequency ultrasound (LFU), as a noninvasive targeted physical therapy, presents a unique advantage in promoting penetration and healing. In addition, our research group found that LFU can enhance the antimicrobial activity against pan-drug resistant bacteria. Therefore, based on the results of synergism effect with antibiotic, the possibility to accelerate the distribution of drug to lung tissue and the potential immune regulation and tissue repair capacity of LFU, we first proposed the idea of "combination therapy of LFU and antibiotic against pulmonary infection caused by drug-resistant bacteria". We designed three levels of experiments on the molecular, cellular and whole animal. Microarray method was applied to comprehensively analyze the molecular mechanism of the immunoregulation and tissue repair. The animal model of pulmonary infection suitable for live imaging system was constructed to achieve intuitive and real-time observation on the degree of infection. The feasibility and mechanism of LFU treatment on pulmonary infection were studied in detail from three aspects: synergism with antimicrobials, promoting drug distribution, immunoregulation and tissue repair. We hope to provide new ideas and methods for the clinical treatment of refractory pulmonary infections.