目的：探讨干眼(DED)发病及其有效治疗的分子机制。

方法：采用超高效液相色谱-四极杆飞行时间质谱(UHPLC-Q-TOF-MS)非靶向技术对18例经药物或针灸治疗的DED患者的泪液样本进行代谢组学研究。

结果：在待测样品中共鉴定出190种代谢物，是迄今为止最广泛的泪液代谢组学研究。结果表明，所有患者的代谢组学特征明显不同，但药物或针灸治疗后的代谢组学差异非常细微。药物治疗后只有6种代谢物发生显著变化，其中肌苷、单胺四乙酸、尿酸盐、丙酰胆碱、烟酰胺等5种代谢物的含量均增加并参与炎症反应。针刺治疗后只有4种代谢物，其中丙氨酸、丝氨酸和高丝氨酸的含量有显著差异。对上述显著变化的代谢物的代谢途径进一步分析表明，针灸治疗的患者只有1种代谢途径，即氨酰tRNA生物合成受到显著影响，这与疾病的病因高度相关，表明针灸疗法可以解决干眼的病因，而不是症状，与药物治疗相比，在一定程度上显示出更好的疗效。

结论：代谢组学分析有助于明确有效治疗干眼的潜在机制中涉及到的关键调控因素或途径，并将有助于为DED治疗提供新的潜在靶点和策略。

METHOD:Here we employed a non-targeted technology, ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UHPLC-Q-TOF-MS), to investigate metabolic characterizations for tear samples from 18 patients with DED upon drug or acupuncture treatment.

RESULTS:A total of 190 named metabolites were identified, which presented so far the broadest tear metabolome. Further analysis indicated a significantly distinct metabolomics profile among all patients, but very subtle metabolic differences upon drug or acupuncture treatment. On one hand, only six significantly changed metabolites were determined after drug treatment, five of which including inosine, monopalmitin, urate, propionylcarnitine, and nicotinamide were all increased and involved in inflammatory responses. On the other hand, merely four metabolites including alanine, serine, and homoserine were found to be significantly different. Further pathway analysis of those six and four significantly changed metabolites revealed that only one pathway, aminoacyl-tRNA biosynthesis was significantly influenced in acupuncture-treated patients, which were highly associated with the cause of the disease. The results here indicated acupuncture treatment may address the cause rather than the symptoms for dry eye disease, displaying partially better compared with drug treatment.

CONCLUSION: Collectively, this work extended our understanding on the key regulatory elements or pathways involved in the potential mechanisms of available effective treatments, and would be useful for providing novel potential targets and therapeutic strategies for DED.