AMPK激动剂在中性粒细胞-MMP-8致真菌性角膜炎炎症损伤中的保护机制

Fungal keratitis is an ocular blindness disease. There are cases still leaving corneal scar even result in blindness after fungi eliminated. How to reduce tissue injury caused by corneal scar and FK blindness is a scientific problem which need to be solved. Based on literature and preliminary data from our research group，a new hypothesis on FK corneal injury and a new idea for therapy have been proposed：Inhibition of AMP-activated protein kinase (AMPK) activity on neutrophils will cause the increased release and activity of Matrix Metalloproteinase-8 (MMP-8) leading to corneal injury in fungal infection site; Application of AMPK agonist can block neutrophils - MMP - 8 pathway to reduce corneal injury. This project intends to study the pathway of neutrophils - MMP - 8 mediated inflammation and corneal injury in FK using the Molecular biology, Immunofluorescence pathologic analysis and the two-photon laser scanning techniques and so on in vitro co-culture system and FK model in AMPK-/-and MMP-8-/- mice. This study will enrich the corneal inflammatory injury theory and provide a new idea and new target for prevention and treatment of corneal injury in FK.

真菌性角膜炎（Fungal keratitis， FK）是一种致盲性眼病，部分病例真菌清除后仍遗留角膜白斑影响视力甚至致盲，如何减轻组织损伤引起的角膜白斑最终降低FK致盲性是待解决的科学问题。在文献和前期研究基础上，我们提出FK组织损伤假说和防治策略：角膜真菌感染后，中性粒细胞上的腺苷酸活化蛋白激酶（AMP-activated protein kinase，AMPK）活性被抑制引起基质金属蛋白酶-8（Matrix Metalloproteinase-8，MMP-8）释放和活性增加，导致角膜损伤；应用AMPK激动剂可以阻断这一通路导致的角膜损伤。本项目通过体外和体内实验，应用分子生物学、免疫荧光、双光子激光扫描等技术，对中性粒细胞AMPK、MMP-8导致的FK组织损伤及应用AMPK激动剂产生的保护机制进行研究，以期丰富FK炎性损伤理论，为临床防治FK引起的组织损伤提供新的防治思路和治疗靶点。