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机械牵拉与前列腺素 E2 联合作用下调圆锥角膜成纤维细胞赖氨酰氧化酶家族基因表达

In order to investigate the effects of mechanical stretching combined with prostaglandin E2 (PGE2) on the gene expression of lysyl oxidases (LOXs) in keratoconus, we treated cultured corneal fibroblasts from healthy human cornea and keratoconus patient cornea with PGE2 and/or cyclic stretch (12% elongation, 0.1 Hz, 12 h). Real-time fluorescent quantitative polymerase chain reaction was used to detect the gene expression of LOXs. The results showed that the gene expression of LOXs in keratoconus group was significantly lower than that in the healthy one. Compared to the static control group, 12% stretching alone up-regulated gene expression of LOXL-2, LOXL-4 in the healthy group, whereas it down-regulated LOXL-3, LOXL-4 in the keratoconus group. Combination of 12% stretching and PEG2 induced LOXL-4 down-regulation in in healthy group, and all LOXs except LOXL-1 in keratoconus group. The results suggested that combination of mechanical stretching and PGE2 down-regulate the gene expression of LOXs in keratoconus. Lower LOXs expression may lead to impaired cross-linking, and thus to a loss of cohesion between collagen fibrils, affecting corneal structural stability by collagen lamellae slippage. This may facilitate the development of keratoconus. Exploring the effects of mechanical stretching and inflammatory factor on the expression LOXs in this paper will help us to understand the possible mechanism of how the keratoconus occurs and develops well, and provide the reference for the prevention and treatment of keratoconus.