β-氨基丙腈对LOX介导的人Tenon囊成纤维细胞外基质过度交联的抑制作用研究

青光眼术后滤过通道瘢痕化是手术失败的主要原因。术后成纤维细胞转分化和细胞外基质过度交联是瘢痕化的两个主要原因。本课题组前期筛选到适配子S58已被证实可抑制人Tenon囊成纤维细胞转分化，但作用有限。我们设想在S58壳聚糖纳米微粒中搭载抑制细胞外基质交联的药物，达到双管齐下的作用，是否能更好地抑制瘢痕形成？术后成纤维细胞过度表达LOX，LOX引起细胞外基质过度交联导致瘢痕化。目前尚无LOX在HTFs中表达情况的研究。β-氨基丙腈是常用的LOX抑制剂，但其能否应用于青光眼术后抗瘢痕中尚有待研究。在该研究中，我们首先观察LOX在HTFs中的表达情况，其次验证β-氨基丙腈是否能够抑制LOX引起的过度交联，如果能够，那么是通过什么途径实现的？CS(S58)-NP搭载β-氨基丙腈后抗瘢痕效果又如何？这都是本研究将要解决的问题。通过本研究，有望进一步优化适配子壳聚糖纳米微粒的抗瘢痕作用。

Scar inhibition of glaucoma filtration surgery (GFS) is one of the key issuesfor the achievement of long-term surgical success.The myofibroblast transdifferentiation and excessive crosslinking of extracellular matrix after surgery are two main reasons leading to subconjunctival scarring. In our previous study, we screened aptamers targeted againstthe extracellular domain of T βRII and derived a dominant sequencecalled aptamer S58 that antagonised TGF-beta-induced transdifferentiation of human Tenon’s capsule fibroblasts into myofibroblastsin vitro. However, the shortage of S58 in the chronergy is existing. We wonder that if CS(S58)-NP could inhibit scarring better by combing drugs for inhibiting excessive crosslingking of extracellular matrix. Fibroblasts overexpress LOX after surgery. The overexpression of LOX causing the excessive crosslinking of extracellular matrix leading to scarring. At present, there is no systematic study on the expression of LOX in HTFs. β-Aminopropionitrile (BAPN) is a commonly used LOX inhibitor, but whether BAPN can be used in glaucoma surgery remains to be studied.In this study, the expression of LOX in HTFs will be studied for the first time. Second, to verify whether BAPN can inhibit LOX induced excessive crosslinking, if so, what is the way to achieve it? How about the anti-scar effect of CS(S58)-NP after combing BAPN? These are the problems to be solved in this study. By the studying of this topic, it is expected to further optimize the anti-scar effect of CS(S58)-NP and to provide experimental evidence for anti-scar therapies after glaucoma surgery.