AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(...AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.展开更多
目的:观察调脂方对动脉粥样硬化(AS)模型小鼠外周血白细胞端粒、端粒酶以及主动脉病变、血脂、炎症指标的影响,探讨其抗AS作用机制。方法: 30只8周龄雄性ApoE -/-小鼠随机分为模型组、阿托伐他汀组、中药干预组,每组10只。另取同周龄雄...目的:观察调脂方对动脉粥样硬化(AS)模型小鼠外周血白细胞端粒、端粒酶以及主动脉病变、血脂、炎症指标的影响,探讨其抗AS作用机制。方法: 30只8周龄雄性ApoE -/-小鼠随机分为模型组、阿托伐他汀组、中药干预组,每组10只。另取同周龄雄性C57BL/6小鼠10只做空白对照组。采用高脂饲料喂养方法建立AS模型,空白对照组、模型组小鼠用蒸馏水灌胃,中药干预组灌服中药“调脂方”,阿托伐他汀组阿托伐他汀钙灌胃给药,持续12周。运用生化仪检测脂代谢指标:总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)及炎症指标:超敏C反应蛋白(hs-CRP)、白介素-6(IL-6);采用油红“O”染色,观察动脉斑块形成及脂质堆积程度;荧光定量聚合酶链反应法检测外周血白细胞及血管细胞的端粒长度及端粒酶活性。结果:与正常空白对照组比较,模型组血清脂代谢指标和炎症指标均明显升高( P <0.01);与模型组比较,阿托伐他汀组和中药干预组均显著降低TC、LDL、HDL、hs-CRP( P <0.01),TG、IL-6( P <0.05);与阿托伐他汀组比较,中药干预组降低TC的作用较弱( P <0.05),而中药干预组在降低TG程度上优于阿托伐他汀组( P <0.05),在降低LDL、hs-CRP、IL-6及升高HDL上无明显差异。主动脉病理油红“O”染色显示模型组AS程度明显,中药干预组和阿托伐他汀组AS程度较模型组明显改善,阿托伐他汀组作用优于中药干预组。模型组外周血白细胞端粒长度明显短于空白对照组、外周血白细胞端粒酶活性低于空白对照组( P <0.05)。与空白对照组比较,中药干预组端粒酶活性、阿托伐他汀组端粒长度、端粒酶活性明显提高( P <0.01),中药干预组与阿托伐他汀组之间外周血白细胞端粒长度及端粒酶活性则无明显统计学差异。结论:调脂方具有抗小鼠AS作用,其机制可能与改善脂代谢、炎症指标及调控端粒长度及端粒酶活性相关。展开更多
基金Supported by Peking Union Medical College Hospital Deposit Integration Commission Funds(No.ZC201904168).
文摘AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.
文摘目的:观察调脂方对动脉粥样硬化(AS)模型小鼠外周血白细胞端粒、端粒酶以及主动脉病变、血脂、炎症指标的影响,探讨其抗AS作用机制。方法: 30只8周龄雄性ApoE -/-小鼠随机分为模型组、阿托伐他汀组、中药干预组,每组10只。另取同周龄雄性C57BL/6小鼠10只做空白对照组。采用高脂饲料喂养方法建立AS模型,空白对照组、模型组小鼠用蒸馏水灌胃,中药干预组灌服中药“调脂方”,阿托伐他汀组阿托伐他汀钙灌胃给药,持续12周。运用生化仪检测脂代谢指标:总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)及炎症指标:超敏C反应蛋白(hs-CRP)、白介素-6(IL-6);采用油红“O”染色,观察动脉斑块形成及脂质堆积程度;荧光定量聚合酶链反应法检测外周血白细胞及血管细胞的端粒长度及端粒酶活性。结果:与正常空白对照组比较,模型组血清脂代谢指标和炎症指标均明显升高( P <0.01);与模型组比较,阿托伐他汀组和中药干预组均显著降低TC、LDL、HDL、hs-CRP( P <0.01),TG、IL-6( P <0.05);与阿托伐他汀组比较,中药干预组降低TC的作用较弱( P <0.05),而中药干预组在降低TG程度上优于阿托伐他汀组( P <0.05),在降低LDL、hs-CRP、IL-6及升高HDL上无明显差异。主动脉病理油红“O”染色显示模型组AS程度明显,中药干预组和阿托伐他汀组AS程度较模型组明显改善,阿托伐他汀组作用优于中药干预组。模型组外周血白细胞端粒长度明显短于空白对照组、外周血白细胞端粒酶活性低于空白对照组( P <0.05)。与空白对照组比较,中药干预组端粒酶活性、阿托伐他汀组端粒长度、端粒酶活性明显提高( P <0.01),中药干预组与阿托伐他汀组之间外周血白细胞端粒长度及端粒酶活性则无明显统计学差异。结论:调脂方具有抗小鼠AS作用,其机制可能与改善脂代谢、炎症指标及调控端粒长度及端粒酶活性相关。
