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载脂蛋白E缺陷小鼠布鲁赫膜的超微结构变化

Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice.

作者信息

Dithmar S, Curcio C A, Le N A, Brown S, Grossniklaus H E

机构信息

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, USA.

出版信息

Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2035-42.

PMID:10892840
Abstract

PURPOSE

To examine the histologic and ultrastructural changes in Bruch's membrane (BM) in apolipoprotein E deficient [ApoE(-)] mice in comparison with age-matched control animals.

METHODS

Two-month-old (group 1) and 8-month-old (group 2) normal control C57BL/6 mice and 2-month-old (group 3) and 8-month-old (group 4) ApoE(-) mice were studied. All groups of mice were fed a standard rodent diet. The mice were killed, serum lipid levels were determined, and the eyes were ultrastructurally examined using standard techniques to measure the thickness of BM. The area fraction of electron-lucent (EL) particles in BM was quantified using point-counting stereology.

RESULTS

The serum cholesterol levels of the ApoE(-) mice were significantly higher than those of the control mice (P = 0.0001). There was a significant thickening and EL particle accumulation in BM associated with age in the control animals. Group 2 had a thicker BM and more EL particle accumulation than group 1 (P = 0.0410 for thickness; P = 0.0042 for particle accumulation). Age-related changes were not seen in ApoE(-) mice; thickness and accumulation were similar in groups 3 and 4 (P = 0.50, thickness; P approximately/= 1.0, accumulation). Significant thickening and accumulation were seen in young ApoE(-) mice (group 3) versus young control animals (group 1; P = 0.008, thickening; P < 0.0001, EL particle accumulation). Group 4 ApoE(-) mice did not have a thicker BM or more EL particles than group 2 control animals (P = 0.2910, thickness; P = 0.35, EL particle accumulation). "Membrane-bounded" material (material between two membranes) was present significantly more frequently in ApoE(-) mice.

CONCLUSIONS

ApoE(-) mice exhibit accumulation of EL particles at an earlier age and have more membrane-bounded material in BM than control mice. This material has ultrastructural similarities to basal linear deposit, which accumulates in age-related maculopathy.

摘要

目的

研究载脂蛋白E缺陷[ApoE(-)]小鼠与年龄匹配的对照动物相比,其布鲁赫膜(BM)的组织学和超微结构变化。

方法

研究2月龄(第1组)和8月龄(第2组)的正常对照C57BL/6小鼠以及2月龄(第3组)和8月龄(第4组)的ApoE(-)小鼠。所有小鼠组均喂食标准啮齿动物饮食。处死小鼠,测定血清脂质水平,并使用标准技术对眼睛进行超微结构检查以测量BM的厚度。使用点计数体视学对BM中电子透明(EL)颗粒的面积分数进行定量。

结果

ApoE(-)小鼠的血清胆固醇水平显著高于对照小鼠(P = 0.0001)。对照动物中,BM存在与年龄相关的显著增厚和EL颗粒积聚。第2组的BM比第1组更厚,EL颗粒积聚更多(厚度P = 0.0410;颗粒积聚P = 0.0042)。ApoE(-)小鼠未见与年龄相关的变化;第3组和第4组的厚度和积聚情况相似(厚度P = 0.50;积聚P约为1.0)。与年轻对照动物(第1组)相比,年轻的ApoE(-)小鼠(第3组)出现显著增厚和积聚(增厚P = 0.008;EL颗粒积聚P < 0.0001)。第4组ApoE(-)小鼠的BM不比第2组对照动物厚,EL颗粒也不比其多(厚度P = 0.2910;EL颗粒积聚P = 0.35)。“膜结合”物质(两层膜之间的物质)在ApoE(-)小鼠中出现的频率显著更高。

结论

与对照小鼠相比,ApoE(-)小鼠在更早的年龄出现EL颗粒积聚,且BM中有更多的膜结合物质。这种物质在超微结构上与年龄相关性黄斑病变中积聚的基底线性沉积物相似。

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