我国是结核病高负担国家，约60%结核性胸腔积液病人残留胸膜纤维化，其发生机制亟待破解。胸腔积液成分复杂，是否有综合多因子、高强度传递细胞间信息的物质，在胸膜纤维化的发生中起关键作用呢？我们预实验收集了46例结核性胸腔积液，提取到大量外泌体，其被胸膜间皮细胞吸收后激活TGF-β/Smad2/3信号通路、上调I型胶原的表达；超声波破坏外泌体明显降低其作用；miRNA测序显示结核性胸腔积液中外泌体miRNA与漏出液比较有明显差异，初步证实其中某些miRNA可能具有直接促纤维化或促进胸膜腔内细胞分泌更多外泌体的作用。因此，我们假设“结核性胸腔积液中外泌体及其所含的miRNA，通过直接促纤维化和促进促纤维化外泌体的不断分泌，介导胸膜纤维化的发生和发展”。因此，我们拟继续收集临床标本，行miRNA测序及其功能鉴定等，深入探讨胸腔积液外泌体促胸膜纤维化的机制，并尝试干预外泌体防治胸膜纤维化的新策略。

China is one of the countries with high burden of tuberculosis. When tuberculous pleural effusions (TBPE) resolve, pleural thickening and fibrosis occurs in about 60% patients, the underlying mechanism remains unknown. Since the constituents and sources of pro-fibrogenic factors in TBPE are complex, is there a key factor which can orchestrate and communicate among the factors and cells? Recently, we collected TBPE from 46 tuberculous pleuritis patients，and collected plenty of exosomes，which can be absorbed by pleural mesothelial cells （PMC） and activated TGF-β/p-Smad2/3 signaling pathway and induced collagen-I synthesis in PMCs. Then we used ultrasonic to break exosomes. These broken exosomes induced less collagen-I synthesis than intact exosomes did. miRNA sequencing showed difference between exosomes from tuberculous pleural effusions and transudate. We preliminary confirmed that some differential expressed miRNAs maybe targeting on genes related with pro-fibrogenic pathway or exosomes biogenesis. Therefore, we hypothesize that “exosomes and contained miRNA in TBPE mediates and promotes tuberculous pleural fibrosis through pro-fibrogenic effect or promote fibrogenic exosomes release”. Hence, we plan to collect more clinical samples, continue to do miRNA sequencing and functional identification, to explore the mechanism of TBPE exosomes in tuberculous pleural fibrosis, and attempt to break exosomes to provide a new strategy in the treatment of tuberculous pleural fibrosis .