ORM1 通过 SPTLC1 对干眼症鞘脂代谢的影响.

Objective To study the effect of ORM1 on sphingolipid metabolism in dry eye via SPTLC1 so as to provide a new research direction for the pathogenesis of dry eye. Methods By the subcutaneous injection of scopolamine hydrobromide (SCOP), a dry eye model was constructed,and adeno-associated virus overexpressing ORM1 was injected through the lens. Tear secretion assay,goblet number,corneal fluorescein staining,lacrimal gland rupture time,and HE assay were performed to assess the corneal conjunctival damage,tear quality,and histopathological changes. Ceramide and sphingomyelin content were detected by biochemical kits, and the expression of ORM1 and SPTLC1 was detected by qPCR and WB. Results (1) ORM1 increased tear secretion in the dry eye model (P< 0.000 1); (2) ORM1 increased the stability of the lacrimal gland on the ocular surface in the dry eye model (P< 0.000 1); (3) ORM1 improved the corneal epithelial damage in the dry eye model (P< 0.000 1); (4) ORM1 increased the number of goblet in the corneal tissue in the dry eye model (P< 0.000 1); (5) After the overexpression of ORM1,the epithelium of the corneal tissue became thicker and the cells of the basal lamina were more closely arranged. cell layers became more numerous and vacuoles were reduced; (6) ORM1 inhibited the inflammatory gene expression in a dry eye model (P< 0.01); (7) ORM1 promoted the total ceramide and sphingomyelin content (P＜0.01); (8) ORM1 promoted the rise of mRNA and protein expression of SPTLC1 (P＜0.001). Conclusion ORM1 can participate in the regulation of sphingolipid metabolism in dry eye disease through the regulation of SPTLC1,which provides new perspectives for exploring the mechanism of the development of dry eye disease and searching for effective and safe therapeutic options. [ABSTRACT FROM AUTHOR]