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国家自然科学基金(30228018)

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Comparative study of histopathology changes between the PS1/APP double transgenic mouse model and Aβ_(1-40)-injected rat model of Alzheimer disease被引量:8
2006年
Objective To identify the genetype of the PS1/APP double transgenic mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenic mice models and Aβ_(1-40)-injected rats models of Alzheimer disease. Methods The modified congo red staining, Nissl's staining and immunohistology staining was used to observe the Aβ deposits, activation of astrocyte respectively. Results ①The PS1/APP transgenic mouse extensively displayed Aβ deposits in the cortex and hippocampal structures, and GFAP positive cells were aggregated in mass and surrounded the congo red-positive plaque. ②The Aβ_(1-40)-intrahippocampal-injected rat model showed the Aβ plaque deposits in the dentate gyrus of the hippocampus, with the astrocyte surrounded. The neurons loss was significant in the injection point and pin hole of injection with Nissl's staining methods. GFAP-positive cells increased significantly compared with the uninjected lateral of the hippocampus. Conclusion Although Aβ_(1-40)-injected rat models could simulate some characteristic pathological features of human Alzheimer diseases, Aβ deposits and neurons loss in partial hippocampal, it would not simulate the progressive degenenration in the brain of AD. The double transgenie PS1/APP mice could simulate the specific pathogenesis and progressive changes of AD, mainly is Aβ deposits and the spongiocyte response, while no neurons loss were observed in this model.
Da-Bing LIJun TANGXiao-Tang FANMin SONGHai-Wei XUYun BAI
关键词:老年性痴呆
CYCLIND1/CDK4在洛伐他汀抑制裸鼠乳腺癌移植瘤增殖中的作用被引量:4
2006年
目的以裸鼠乳腺癌异种移植瘤动物模型为研究对象,检测了洛伐他订(LOV)对高表达BRCA1基因乳腺癌异种移植瘤生长能力的影响,并初步探讨了其作用的分子机制。方法将PCDNA3-BETA-HA-HSBRCA1质粒进行扩增、鉴定后,运用脂质体转染MCF-7乳腺癌细胞,经RT-PCR、WESTERN BLOTTING鉴定转染后BRCA1的表达,以2×106个MCF-7、MCF-7BRCA1细胞接种BALB/C裸鼠,建立乳腺癌细胞异种移植瘤动物模型,肿瘤生长4周后,皮下注射LOV[50MG/(KG.D)]10D,检测肿瘤的增殖能力和组织病理学变化,RT-PCR、WESTERN BLOTTING检测CYCLIND1、CDK4MRNA及蛋白表达。结果裸鼠分别接种MCF-7、MCF-7BRCA1细胞后均能长出肿瘤,成瘤率为100%,组织病理切片观察其生物学特性没有发生改变;经LOV干预10D后,MCF-7细胞和MCF-7BRCA1细胞移植瘤体积均缩小,移植瘤内CYCLIND1、CDK4MRNA及蛋白表达降低;癌细胞数减少,坏死灶增多,且MCF-7BRCA1细胞移植瘤组变化更明显。结论洛伐他汀明显阻滞高表达BRCA1基因乳腺癌异种移植瘤的生长、增殖,这可能与移植瘤组织内CYCLIND1、CDK4表达的降低有关,该效应提高了乳腺癌异种移植瘤对洛伐他汀的敏感性,增强了洛伐他汀的抗肿瘤作用。
罗远琼糜漫天
关键词:洛伐他汀乳腺癌异种移植瘤增殖细胞周期调控蛋白
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