基于“microRNA146a/IRAK1/JNK1”信号通路阐明“益气生津法”对混合型干眼的效应机制

干眼是目前影响视觉与生活质量最常见的眼表疾病，干眼的研究一直是眼科专业领域的焦点，久视已被证实为干眼的独立危险因素。本项目从“气虚津亏”的独特视角对久视所致干眼进行探究，提出“竭视劳瞻，导致气虚，气不生津行津摄津，泪液动力学异常及蒸发过强，而发津亏，泪液高渗，激活miR-146a/IRAK1/JNK1信号通路，促进炎性因子释放与角膜上皮细胞凋亡，降低泪膜稳定性。而益气生津法可能通过调节miR-146a/IRAK1/JNK1通路对干眼起到防治作用”的科学假说。通过双眼持续固视结合强气流复制混合型干眼大鼠模型，给予益气生津中药干预，观察大鼠泪膜稳定性及角膜上皮超微形态改变，从角膜miR-146a/IRAK1/JNK1通路的调控，阐明干眼的炎性反应机制及益气生津法的防治机制，揭示“气虚津亏”的科学内涵，丰富中医气津理论及治则治法，对久视所致干眼的因机证治研究进行补充，也为其临床防治提供实验依据。

As the most common ocular surface disease, dry eye not only affects vision but also seriously affects the quality of life. Therefore, the research of dry eye has always been the focus of the ophthalmology professional field. Long time watch has been confirmed as an independent risk factor for dry eye. Exploring the mixed dry eye caused by long time watch from the unique perspective of “Qi deficiency”, scientific hypothesis that exhaustion of hard work leads Qi deficiency is put forward. In other words, Qi does not produce body fluid, which leads to abnormal tear fluid dynamics and excessive evaporation. At the same time, insufficiency of body fluids promotes tear hypertonicity and activates the miR-146a/IRAK1/JNK1 pathway. With inflammatory factors released, ocular surface inflammation and corneal epithelial cell apoptosis is aggravated, there by reducing tear film stability, and clarify the curative effect mechanism of enhancing Qi while nourishing fluid method. By giving the mixed dry eye rat model with double-eye continuous fixation combined with strong airflow to reproduce the traditional Chinese medicine intervention of enhancing Qi while nourishing fluid method, the stability of the rat's tear film and the changes of corneal epithelium ultra-micromorphology are observed. Therefore, the mechanism of inflammation and apoptosis of dry eye as well as enhancing Qi while nourishing fluid method is clarified by the regulation of corneal miR-146a/IRAK1/JNK1 pathway. Furthermore, the scientific connotation of "deficiency of Qi and body fluid" was revealed. At the same time, the theory of Qi and body fluid in TCM and its treatment methods were enriched, which can not only supplement the research on the cause and treatment of dry eye caused by long time watch, but also provide experimental basis for its clinical prevention and treatment.