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Int J Mol Med ; 46(1): 340-350, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32626913

RESUMO

The present study aimed to investigate the protective effects exerted by astragaloside­IV (AIV) on retinal pigment epithelial (RPE) cells of rats with diabetes mellitus (DM), and to explore the underlying molecular mechanisms. For this purpose, a rat model of DM was established by injecting rats with an intraperitoneal injection of streptozotocin. AIV was then intragastrically administered. An electroretinogram (ERG) was used to assess retinopathy and TUNEL staining was used to detect the level of apoptosis of RPE cells. Western blot analysis was used to determine protein expression in RPE cells in vitro and in vivo. AIV was found to be able to significantly increase body weight and decrease blood glucose levels in rats with DM in a dose­dependent manner. Compared with the rats with DM, the rat rod cell response a wave, b wave, maximum response b wave, photopic (photo)­ERG b wave and oscillatory potential (OP) p4 wave latency significantly decreased and the amplitude of OP Os1 wave increased significantly in the rats with DM treated with AIV for 11 weeks. In addition, AIV significantly decreased the apoptotic levels of RPE cells from rats with DM and significantly decreased the protein expression levels of Bax/Bcl­2, Fas/FasL, active caspase­3, active caspase­8, active caspase­9, homeobox B3 (HOXB3), p­phosphoinositide 3­kinase (PI3K)/PI3K, p­AKT/AKT and p­p70S6K1/p70S6K1, whereas it significantly increased miR­128 expression in the RPE cells from rats with DM. In vitro, AIV significantly inhibited the high glucose (HG)­induced apoptosis of RPE cells by increasing miR­128 expression and Bcl­2 and FasL protein expression in vivo. On the whole, the findings of the present study demonstrate that AIV treatment protects RPE cells of diabetic rats from apoptosis, and that these effects may be associated with the upregulation of miR­128 expression.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Saponinas/farmacologia , Saponinas/uso terapêutico , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Astrágalo/química , Western Blotting , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Diabetes Mellitus Experimental/metabolismo , Proteína Ligante Fas/metabolismo , Feminino , Citometria de Fluxo , Marcação In Situ das Extremidades Cortadas , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Saponinas/química , Triterpenos/química
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