血脂异常ApoE基因缺失小鼠视网膜及Bruch膜组织形态观察

Morphological characteristics of retina and Bruch’s membrane in apolipoprotein E-deficiency (ApoE/-) mice with dyslipidemia

目的观察血脂异常ApoE基因缺失(apolipoprotein E-deficient,ApoE-/-)小鼠视网膜和Bruch膜组织形态改变。方法采用随机数字表法根据小鼠体质量分层随机分组。将24只2月龄(ApoE-/-)小鼠分为高脂组和普食组,另用12只2月龄C57BL小鼠作为普食对照组,喂养4个月后检测血浆总胆固醇(totalplasma cholesterol,TC)、低密度脂蛋白(low density lipoprotein,LDL),光镜和电镜观察视网膜和Bruch膜的组织形态改变,光镜下半定量检测视网膜光感受器细胞、色素上皮细胞(retinal pigment epithelium,RPE)数量。结果与普食对照组相比,6月龄ApoE-/-高脂组小鼠的TC、LDL明显增高(P<0.001),同时视网膜光感受器细胞、RPE排列紊乱、萎缩、数量明显减少(P<0.001),Bruch膜粗细不等、纤维分叉、厚度明显增厚(P<0.001),部分小鼠视网膜下可见玻璃膜疣形成。电镜观察RPE基底膜皱褶变短且减少,胞质内线粒体肿胀,胞浆中可见大量空泡,Bruch膜明显变厚,纤维结构明显减少,弹力层断裂。结论血脂异常ApoE-/-小鼠视网膜、Bruch膜出现的组织形态改变符合年龄相关性黄斑变性的病理改变,该动物模型可用做年龄相关性黄斑变性的研究。

OBJECTIVE To observe morphological characteristics of retina and Bruch’s membrane in apolipoprotein E-deficiency（ApoE-/-） mice with dyslipidemia.METHODS Twenty-four apolipoprotein E deficiency（ApoE-/-） mice at two-month age were randomly divided into high fat diet group and normal diet group,and 12 C57BL mice were chosen as normal diet control group.After being fed for 4 months,total plasma cholesterol（TC） and low density lipoprotein（LDL） were determined,morphological characteristics of retina and Bruch’s membrane were observed under light and electron microscope,and amounts of retinal photoreceptor cells and pigment epithelial cells（RPE） were examined by semi-quantitative histopathology.RESULTS Compared with normal diet control group,TC and LDL were significantly increased in high fat diet group（P〈0.001）.Under light microscope,retinal photoreceptor cells were disorganized,atrophic and reduced in high fat diet group（P〈0.001）,and changes of disturbance,randomly oriented fiber and thickening could be seen in Bruch’s membrane（P〈0.001）,in addition,retinal drusen were formed in partial mice.Under electron microscope,shortening and destruction in basal infolding of basement membrane,swelling of mitochondria,and vacuoles could be observed in RPE,as well as thickening of Brunch membrane with decrease in fiber and rupture in elastin layers.CONCLUSIONS Morphological changes in retina and Bruch’s membrane of ApoE-/-mice with dyslipidemia were in accordance with age-related macular degeneration;therefore,it could be adapted to research age-related macular degeneration.