代谢综合征干扰角膜自稳态和创伤修复过程的分子和细胞机制

目前因营养过剩而造成的代谢综合征和肥胖问题已构成全球严重的公共健康问题。研究表明，一旦进入晚期并发症，干预措施则很难奏效。因此，在发生II型糖尿病之前尽早实施某些预防措施将至关重要。但该综合征所导致的角膜结构和功能以及对创伤修复过程的影响还不清楚。我们初步的研究结果显示：高脂饮食（HFD）可导致角膜上皮变性、神经密度和触觉功能显著下降、创伤修复过程显著延迟。本项目旨在使用HFD致代谢综合征小鼠模型：（1）确定HFD致代谢综合征对角膜早期结构、生理功能和昼夜节律等自稳态的影响；（2）分析代谢综合征状态对正常角膜创伤修复后级联反应过程的影响；(3) 寻找导致上述角膜病理性改变和角膜创伤修复过程延迟的细胞和分子机制；（4）通过药理性干预措施和改变饮食寻找潜在的改善上述病情或加速修复过程的靶向性治疗措施。

Currently the metabolic syndrome and obesity problems caused by over-nutrition have posed a serious global public health problem. Studies have shown that, once advanced complications, intervention is difficult to work. Therefore, it is important to implement some precautionary measures early in the event of type II diabetes. But impacts of the syndrome on the corneal structure and function and corneal wound repair process are unclear. Our preliminary study showed that high-fat diet (HFD) can lead to corneal epithelial degeneration, nerve density and tactile function decreased significantly, the trauma repair process significantly delayed. The aim of this study was to use the HFD-induced metabolic syndrome mouse model: (1) to determine the effect of HFD-induced metabolic syndrome on the early structural, physiological function and circadian rhythm of the cornea; (2) to analyze effects of the metabolic syndrome on cascade response of corneal wound healing. (3) to explore the cellular and molecular mechanisms leading to the above-mentioned corneal pathological changes and delays in the repair of corneal trauma; (4) to seek a potential targeted therapy for improvement of the pathologic condition by pharmacological interventions and diet switching to accelerate the repair process of the cornea.