Effect of S1PR1 on Blood-Labyrinth Barrier Permeability in Aged C57BL/6J Mice
YU Meng1,2, YU Miao2,3, SUN Shiheng2, WANG Haoyang2, ZENG Xiansi2, LIU Zhidan2, JIANG Wenjun1,2, LI Li1,2*
In this study, the paper examined the expression of S1PR1 in stria vascularis of C57BL/6J mice at different ages to explore the effect of S1PR1 on the permeability of blood-labyrinth barrier in endothelial cells of stria vascularis of the aged cochlea. ABR (auditory brain response) was used to measure auditory function. Evans blue staining for the permeability of the cochlear blood-labyrinth barrier. The expression of S1PR1 and connexin in stria vascularis of cochlea was detected by immunofluorescence. The release of S1P was detected by ELISA. The permeability of endothelial cells was measured by Transwell chamber. The expression levels of S1PR1 and tight junction protein in EC were detected by Western blot. The results showed that the hearing threshold and high frequency hearing loss were significantly increased in the 12m group, the permeability of cochlear blood-labyrinth barrier was increased, and the expression levels of S1PR1 and tight junction protein were decreased. At the cellular level, the release of S1P and the expression of S1PR1 were decreased in the D-gal+EC group, and S1PR1 expression was increased after the addition of exogenous S1P, while the expression of tight junction protein was decreased and endothelial permeability was increased in the D-gal+EC group, when exogenous S1P was added, tight junction protein expression was increased and endothelial permeability was decreased. When S1PR1 inhibitor was given, tight junction protein expression was decreased and endothelial permeability was increased. The decrease of S1PR1 expression in vascular stria endothelial cells of the cochlea during senescence may down-regulate the expression of tight junction protein, and then affect the permeability of blood labyrinth barrier.
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