氧化应激及相关脂肪酸代谢在睑板腺功能障碍发病中的作用及机制研究

睑板腺功能障碍（MGD）是蒸发过强型干眼的主要病因，患病人群基数大且显著影响患者生活质量。近期研究表明氧化应激和脂质成分异常均与MGD发病存在联系，但其具体分子生物学机制未明。我们在前期工作中发现：氧化应激可引起该细胞线粒体膜电位下降、细胞凋亡率升高；细胞内长链饱和脂肪酸（PSFA）含量上升；MAPK/JNK、MAPK/ERK通路激活；PSFA处理细胞也可激活细胞MAPKs通路。综上，本课题组首次提出氧化应激可能通过PSFA和MAPKs部分信号通路的方式启动细胞凋亡程序从而参与MGD的发生发展。我们拟研究氧化应激下，睑板腺上皮细胞PSFA表达、JNK和ERK信号通路及凋亡的变化规律；明确相关靶向基因；并通过抗氧化应激缺陷小鼠、PSFA合成异常小鼠明确“氧化应激-脂质代谢-MAPKs信号通路”轴在MGD中的作用机制，为临床上治疗MGD提供新的理论依据和实验基础。

Meibomian gland dysfunction (MGD) is the main cause of evaporative dry eye syndrome, leading to the decreased quality of life in patients. Recent studies have shown that oxidative stress and lipid abnormalities were associated with the onset of MGD, however, the exact mechanism remains elusive. We found as shown in below in our previous work: oxidative stress decreased the mitochondrial membrane potential and increased the apoptosis rate; the component of long chain polysaturated fatty acids (PSFA) raised in cells; lead to the MAPK / JNK and MAPK / ERK pathway activation; PSFA treated cells also could activate cells MAPKs pathway. In summary, we first proposed that oxidative stress initiates the apoptosis and thus participates in the development of MGD via PSFA and MAPKs signaling pathway. This project intends to explore the relationship among oxidative stress, PSFA, MAPK/JNK and MAPK/ERK signaling pathway, and apoptosis; explore the potential target genes; and use SOD1 knock-out mice, Stgd3 mice to discuss the role of the axis of oxidative stress - PSFA -MAPKs signaling pathway in MGD, in order to provide new insight and experimental basis for novel therapies for MGD.