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目錄

動脈粥樣硬化模型

LDL knockout小鼠(LDLR-deificient mouse)

LDL受體基因小鼠

動脈粥樣硬化造模和模型飼料



LDL受體基因敲除(LDLR-/-)小鼠
動脈粥樣硬化造模和模型飼料要求
Model Diet of Atherosclerosis for LDLR-/- Mice


LDL受體(low density lipoprotein receptor, LDLR)敲除小鼠是目前在動脈粥樣硬化(AS)研究領域中應用最多的基因工程動物之一。該小鼠對脂肪和膽固醇都非常敏感,因此,要根據研究目的選擇相應的模型飼料和造模。

除非實驗有特殊要求,應當選用基于C57BL/6小鼠為母本(野型)敲除LDLR的小鼠。

一、LDLR敲除小鼠動脈粥樣硬化的特點


1.LDLR敲除小鼠動脈粥樣硬化動物模型的優勢

(1)研究LDLR在動脈粥樣硬化發生中的表現和作用;

(2)與ApoE基因缺陷小鼠相比,LDLR-/-小鼠脂蛋白譜更近似于人類,有利于將脂蛋白改變與人類動脈粥樣硬化與高脂血癥的關系進行推演;有助于觀察藥物或者食品功能因子干預后分析脂蛋白改變的臨床意義。

(3)在喂養普通飼料時不會自發地發生或者發生非常輕微的動脈粥樣硬化。這有利于模型飼料組與正常組之間的可比性更強。

(4)血漿膽固醇對飼料中膽固醇很敏感,可通過改變飼料中膽固醇含量控制血漿膽固醇水平,使病變更接近人類病變。

(5)動脈粥樣硬化可以發展到纖維化斑塊或者纖維帽階段,因此,可以模擬人類動脈粥樣硬化的所有階段。

2.LDLR敲除小鼠動脈粥樣硬化動物模型的缺點

(1)要形成動脈粥樣硬化高級階段,需要喂養的時間較長。

(2)伴有脂肪肝等異常。

(3)與其他所有基因工程動物相同:都是非正常動物,研究結果難以推演到人類疾病以及藥物或者食品功能因子對人類動脈粥樣硬化的效果。

二、LDLR敲除小鼠動脈粥樣硬化造模對飼料的要求和選擇方法


(1)日常喂養的飼料要求很高

雖然LDLR敲除小鼠沒有ApoE敲除小鼠那樣容易自發性動脈粥樣硬化,但是,如果日常喂養的普通飼料含有膽固醇和飽和脂肪較多,可以引起自發性高膽固醇血癥和動脈粥樣硬化。因此,一般的大鼠或小鼠的普通不宜采用。

建議采用南通特洛菲飼料科技有限公司有限公司生產的特別適用于脂蛋白代謝及相關基因的基因工程小鼠的普通喂養飼料,詳細了解請點擊:LAD0011介紹

(2)模型飼料中膽固醇水平要適度

由于對飼料膽固醇非常敏感,血液膽固醇濃度與飼料膽固醇含量成比例升高,如果模型飼料中采用膽固醇較高,可能發生嚴重的高膽固醇血癥,引起膽固醇毒性,不僅增加動物死亡率,而且不符合人類的動脈粥樣硬化的血脂情形。

(3)脂肪含量的確定和控制

LDLR敲除小鼠對脂肪含量敏感,對脂肪類型或不同脂肪酸比例的構成也非常敏感。在使用高膽固醇飼料時脂肪含量和脂肪類型應當科學地確定。在選擇高脂高膽固醇飼料時,要對脂肪含量和脂肪類型進行謹慎地選擇。

(4)除非研究中有特殊要求,模型飼料不應當添加膽鹽

膽鹽添加可導致伴有炎癥的動脈粥樣硬化,除非研究特別需要,例如,觀察藥物對動脈粥樣硬化的干預作用,或者研究膽鹽的作用,模型飼料不應當選擇添加膽鹽。

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