LncRNA H19/miR-675轴靶向调控“治节重建”干预COPD肺血管重构的机制研究

“肺主治节”是对肺生理功能的高度概括，其治节功能通过肺主气行使。肺气虚则治节失常，可致气虚痰凝血瘀，迁延日久导致肺系脉络失常，甚至痹阻，与现代医学COPD肺血管重构病理表现极为相似。既往研究表明，益气化痰祛瘀方药能重建肺的治节功能，改善肺血管重构。我们借助高通量测序发现，LncRNA H19/miR-675轴表达在COPD肺组织显著上调，与PASMCs异常增殖密切相关，是调控COPD肺血管重构的重要靶点，机制有待进一步探明。鉴此，项目围绕“益气化痰祛瘀方介导LncRNA H19/miR-675轴，调控治节重建，抑制PASMCs增殖，影响肺血管重构进程”的假说，拟采用体内外结合的研究方法，运用双荧光素酶报告基团检测、基因干扰和过表达等技术，以LncRNA H19/miR-675轴视角，探讨COPD肺血管干预机制，阐释益气化痰祛瘀方调控“治节重建”的科学内涵，为COPD防治提供新的证据和支持。

The “lung governing coordinative activities of viscera” comprehensively summarized the physiological functions of the lungs, and it is executed via lung governing qi. Lung qi deficiency results in the “lung failure coordinative activities of viscera”, which leads to the “qi deficiency, coagulation, and phlegm”, and eventually brings pulmonary dysfunction and even stagnation. This phenomenon is similar to the pathological manifestations of pulmonary vascular remodeling in COPD. It has been proved that Yiqi Huatan Quyu recipe could effectively reconstruct the pulmonary vascular and the function of the lungs. Combining with the high-throughput sequencing, we have found that the expression of LncRNA H19/miR-675 axis is significantly up-regulated in COPD lung tissue, which is closely related to the abnormal proliferation of PASMCs, and may be an important target for the regulation of COPD vascular remodeling. Nevertheless, the mechanism needs further exploration. Therefore, we hypothesize that Yiqi Huatan Quyu recipe may regulate the expression of LncRNA H19/miR-675 axis to inhibit the proliferation of PASMCs, reconstruct the function of the “lung governing coordinative activities of viscera”and further affect the process of pulmonary vascular remodeling. From the perspective of LncRNA H19/miR-675 axis, we will protocol the study of in vitro and in vivo, also combined research methods including detecting techniques like dual luciferase reporter detection, gene interference, overexpression, etc., to explore the mechanism of pulmonary vascular regulation in COPD, and explain the scientific connotation on the reconstruction of “lung governing coordinative activities of viscera” via Yiqi Huayu Recipe. We hope to provide a new evidence to support the prevention and treatment of COPD.