淋巴循环在淋巴管肌瘤病（LAM）的特征、机制与创新治疗研究

淋巴管肌瘤病（lymphangioleiomyomatosis，LAM）是一种罕见的以肺部弥漫性囊性病变为特征的多系统肿瘤性疾病，以散发形式或遗传性疾病结节性硬化症（tuberous sclerosis coplex, TSC）相关的形式出现。约20%的患者出现淋巴循环异常的临床表型。前期我们发现血液中血管内皮生长因子-D（VEGF-D）增高与淋巴循环受累表型以及TSC患者肺部出现LAM病灶密切相关，通过特异性分子探针68Ga-NEB介导的PET/CT淋巴显像方法首次揭示肺部淋巴循环存在广泛异常。基于这些研究，我们假设淋巴循环异常是LAM的一个关键发病机制。基于现有队列，本研究设立淋巴循环研究亚组（100例），整合临床、影像、淋巴循环显像和肺病理等精准淋巴循环评估信息，揭示淋巴循环在LAM和TSC的特征与意义。并通过细胞和动物模型研究淋巴循环异常在LAM的分子机制以及潜在新治疗。

Lymphangioleiomyomatosis (LAM) is a rare multi-system neoplastic disease with a characteristic of diffuse cystic changes in the lung. It is sporadic or associated with a genetic disorder - tuberous sclerosis complex (TSC). About 20% of LAM patients present a clinical subtype of abnormal lymphatic circulation, such as chylothorax, or retroperitoneal lymphangioleiomyomas. We established a cohort of LAM and TSC registry, found vascular endothelial growth factor – D (VEGF-D) increased and correlated with abnormal lymphatic presentations. We also first demonstrated existence of diffuse lymphatic changes in lung with a high sensitive nuclear imaging with a probe of 68Ga-NEB. We hypothesized that lymphatic dysfunction may be a key mechanism in pathogenesis of LAM and we presumed that correction for abnormal lymphatic circulation would be a novel treatment for LAM. The proposed study will explore the clinical characteristics and significant of lymphatic circulation in LAM by establishing a cohort of 100 LAM patients which will provide systematical and precise investigations of clinical, pathological and radiological manifestations of lymphatic circulation. We will also investigate the role of lymphatic circulation in LAM development using cell and animal models, and investigate the potential application of anti-lymphatic dysfunction as novel therapeutic strategy in LAM.