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Carnosol Alleviates Oxidative Stress-induced Retinal Neuroinflammation

Posted on:2021-01-10Degree:MasterType:Thesis
Country:ChinaCandidate:L Y WuFull Text:PDF
GTID:2404330623468116Subject:Biochemistry and Molecular Biology
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ObjectiveMany diseases can cause retinal damage.In addition to primary retinal nerve injuries such as glaucoma and age-related macular degeneration,more and more studies have shown that systemic or extra-ocular organ diseases(especially metabolic and immune diseases)can also be associated with retinal nerve injuries.Diabetes mellitus,multiple sclerosis,inflammatory bowel disease(IBD),and other inflammatory markers were found to be associated with retinal nerve damage.In addition,in the previous study,our team found that the retinal neurons of mice model of acute colitis were lost,and Microglia activation of innate immune cells was also detected,suggesting that neuroinflammation was involved in retinal nerve injury.At the same time,we also detected upregulation of HIF-a expression in this model,suggesting that oxidative stress is involved in retinal nerve injury.In recent years,the use of natural metabolites to prevent disease has aroused wide interest.Carnosol(CA)is a polyphenol found in rosemary extract,which has antiinflammatory,antioxidant and other bioactive functions.Therefore,the effect and molecular mechanism of Carnosol on retinal oxidative stress and oxidative stress were investigated.PurposeTo investigate the effect of Carnosol on oxidative stress and neuroinflammation of retina and its molecular mechanism.Method30 adult mice were randomly divided into 3 groups:(1)normal control group(H2O): normal diet without special treatment;(2)DSS model group: free drinking of 1.5%DSS solution for 7 days for modeling,and then drinking water for 3 days;At the same time,daily injection of PBS solution;(3)DSS+Carnosol group: drinking 1.5%DSS solution freely for 7 days to make mold,and then changing to drinking water for 3 days;Also inject Carnosol solution daily.The general condition of the mice was observed daily for the disease activity index(DAI)score.The colonic retinas of three groups of mice were observed on the 10 th day.Paraffin HE staining was used to detect colonic mucosal injury.The intestinal epithelial barrier was detected by fluorescence immunostaining.Apoptotic proteins were detected by Western blot.The expression levels of inflammatory factors and hif-1α in retina were detected by real-time fluorescent quantitative PCR.ResultThe previous study of our group found that the retinal kernel layer of mice with acute colitis was thinner and the bipolar cells and ganglion cells were lost.DAI scores show that;Carnosol reduced DAI scores in colitis mice.Pathological staining of the colon showed that;Carnosol reduced the extent of mucosal damage to the colon.The results of fd-4 intestinal epithelial permeability test and serum lipopolysaccharide(LPS)detection showed.Intestinal permeability decreased and serum LPS decreased after Carnosol treatment.Fluorescence immunostaining results showed that;Carnosol significantly reduced the infiltration of inflammatory cells in the intestinal lamina propria and the loss of e-cadherin proteins in the intestinal epithelium.Annexin-v PI double staining and in vitro LPS stimulation of intestinal epithelial cells were shown.Carnosol can reduce the apoptosis of intestinal epithelial cells.Fluorescence quantitative PCR results showed that;The expression levels of retinal inflammatory factor and hif-1α were down-regulated in colitis mice.ConclusionNeurons were damaged in mice model of enteroretinal nerve injury.Early neuroinflammation and oxidative stress were present in this model.The anti-inflammatory effect of Carnosol was verified in the intestinal tract.Carnosol alleviated retinal inflammation in the model mice.Carnosol alleviated oxidative stress in the retina of the model mice...
Keywords/Search Tags:Carnosol, oxidative stress, retinal inflammation, IBD, HIF-1α
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