Effect and mechanism of bisphenol A and high fat diet on retinal microvessels/capillaries in mice
Objective To investigate the effect and mechanism of bisphenol A(BP A)and high fat diet on retinal microvessels/capillaries angiogenesis and apoptosis in mice.Methods Sixty female C57BL/6J mice aged 6-8 weeks were randomly divided into six groups:solvent control group(C0),high-fat group(C1),standard diet with 0.05 mg/kg·bw/d BP A group(C2),and high-fat diet with 0.005 mg/kg·bw/d BPA group(TL),0.05 mg/kg·bw/d BPA group(TM),0.5 mg/kg·bw/d BP A group(TH).After 90 days,the mice were executed under anesthesia and samples were taken for testing.Contents of TG,TC,HDL,LDL and GLU in serum were detected by automatic chemiluminescence immunoassay.The morphological changes of retinal capillaries were observed on retinal tissue sheet.HE staining was used to observe the pathological changes of retinal tissue.The expression levels of VEGF,VEGFR2,P-AKT,eNOS,Bax,Bcl-2 and Caspase-3 proteins were detected by immunohistochemistry.The apoptosis of retinal tissue cells was detected by TUNEL method.Results The combined intervention of BPA and high-fat diet can affect the morphology and structure of retinal capillaries,and make the thickness of retina,optic fiber layer and inner retinoid layer thinner,and significantly increase the levels of TC,HDL and GLU in the intervention groups which were excluded C2 group(FTC=17.874,FHDL=19.568,FGLU=20.983;P<0.05),the protein levels of VEGF,VEGFR-2,eNOS,Bax and Caspase-3 were significantly increased in all intervention groups but TL group.All intervention groups down-regulated the protein levels of Bcl-2,and significantly increased the apoptosis of retinal cells in each intervention group(F=2.995,P<0.05).Conclusion BPA and high-fat diet may induce apoptosis of retinal microvessels/capillaries and angiogenesis in mice,and VEGF/VEGFR2/eNOS pathway may be one of the mechanisms.