Arjunolic acid protects diabetic retinopathy by regulating autophagy through the AMPK/mTOR/HO-1 signaling pathway
Objective To investigate the effects of arjunolic acid(AA)on autophagy and the AMP-activated protein kinase(AMPK)/mechanistic target of rapamycin(mTOR)/heme oxygenase-1(HO-1)signaling pathway in retinal cells of rats with diabetic retinopathy(DR).Methods A streptozotocin(STZ)-induced diabetic rat model was constructed in healthy Sprague-Dawley(SD)rats.Rats were randomly divided into control(Con)group,model(STZ)group,low-dose AA(AAL,10mg/kg)group and high-dose AA(AAH,10mg/kg)group.After 10 weeks of the continuous intervention,H&E staining was performed to detect retinal histopathological structures.The quantitative reverse transcriptase PCR(qRT-PCR)was performed to detect mRNA expressions of interleukin(IL)-1β,IL-6 and mitochondrial pyruvate transporter(MPC)-1 in retinal tissues.Dihydroethidium(DHE)staining was performed to assess the production of reactive oxygen species(ROS)in retinal tissues.Western blot was performed to detect autophagy proteins and those in the AMPK/mTOR/HO-1 signaling pathway.Results Compared with those of the Con group,rats in STZ group presented pathological changes like Retinal swelling and vacuolar degeneration,significantly lower thickness of the outer nuclear layer(ONL)of the retina,nuclear counting,light chain3/1(LC3Ⅱ/Ⅰ)ratio and protein levels of HO-1and p-AMPK/AMPK,but significantly higher mRNA levels of IL-1β,IL-6 and MCP-1,ROS levels in the ONL,inner nuclear layer(INL)and ganglion cell layer(GCL),and protein levels of p62 and p-mTOR/mTOR(P<0.01).Compared with those of STZ group,ONL thickness and nucleus count of rats in the AAL group and AAH group were significantly higher(P<0.05),with a relatively intact retinal structure.Compared with those of AAL group,rats in the AAH group presented significantly lower mRNA levels of IL-1β,IL-6 and MCP-1,ROS levels in the ONL,INL and GCL,and protein levels of p62 and p-mTOR/mTOR,but significantly higher LC3Ⅱ/Ⅰ ratio and protein levels of HO-1 and p-AMPK/AMPK(P<0.05 or P<0.01).Conclusion AA may be a promising candidate for the treatment of DR,which protects retinal cells from STZ-induced oxidative stress and inflammatory damage through regulating cell autophagy via the AMPK/mTOR/HO-1 signaling pathway.
ajmalonic aciddiabetic retinopathyAMP-activated protein kinase(AMPK)/mechanistic target of rapamycin(mTOR)/heme oxygenase-1(HO-1)pathwayautophagy
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