首页|双酚A和高脂饮食对小鼠视网膜微血管/毛细血管的影响及机制研究

双酚A和高脂饮食对小鼠视网膜微血管/毛细血管的影响及机制研究

扫码查看
目的 探讨双酚A(bisphenol A,BPA)和高脂饮食对小鼠视网膜微血管/毛细血管血管新生及细胞凋亡的影响及机制.方法 选用60只6~8周龄雌性C57BL/6J小鼠,随机分为6组:溶剂对照组(C0)、高脂组(C,)、标准饲料且 0.05 mg/kg·bw/d BPA 组(C2)、高脂饲料且 0.005 mg/kg·bw/d BPA 组(TL)、0.05 mg/kg·bw/d BPA 组(TM)、0.5mg/kg·bw/d BPA组(TH).90 d后,麻醉处死小鼠并留取样品进行检测.采用全自动化学发光免疫分析仪检测血清中TG、TC、HDL、LDL和GLU含量;采用视网膜组织铺片观察视网膜毛细血管的形态变化;采用HE染色观察视网膜组织病理变化;采用免疫组化检测视网膜组织VEGF、VEGFR2、P-AKT、eNOS、Bax、Bcl-2和Caspase-3蛋白水平;采用TUNEL法检测视网膜组织细胞凋亡情况.结果 BPA和高脂饮食共同干预可影响视网膜毛细血管形态及结构,各干预组(C2组除外)出现视网膜、视神经纤维层、内从状层厚度变薄和血清中TC、HDL、GLU水平上升(FTC=17.874,FHDL=19.568,FGLU=20.983;P<0.05);各干预组(TL组除外)VEGF、VEGFR-2、eNOS、Bax和Caspase-3蛋白表达水平明显上调,各干预组Bcl-2蛋白水平均明显下调,各干预组小鼠视网膜组织细胞凋亡与对照组相比明显增高(F=2.995,P<0.05).结论 BPA和高脂饮食可诱导小鼠视网膜微血管/毛细血管血管凋亡及存在诱导血管新生的趋势,VEGF/VEGFR2/eNOS通路可能是其机制之一.
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.

Bisphenol AHigh-fat dietMicrovascularCapillariesAngiogenesis

徐兰兰、姚瑞娟、陆泽琪、齐从政、张姣香、黄冰、张岩、李文学、杨光宇、朱伟

展开 >

广州医科大学公共卫生研究院,广州市疾病预防控制中心,广东广州 510440

双酚A 高脂饮食 微血管 毛细血管 血管新生

广州市医学重点学科广州市重点研发计划广州市基础与应用基础重点实验室

202120230122022060800142024A03J0558

2024

毒理学杂志
北京市预防医学研究中心 北京大学医学部公共卫生学院

毒理学杂志

CSTPCD
影响因子:0.504
ISSN:1002-3127
年,卷(期):2024.38(4)
  • 4