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动脉粥样硬化模型

ApoE敲除小鼠(ApoE-deificient mouse)

ApoE基因敲除或沉默小鼠

动脉粥样硬化造模和模型饲料



ApoE基因敲除小鼠动脉粥样硬化模型的造模和复制方法
Atherosclerosis Model in ApoE-knockout Mouse

一、ApoE敲除小鼠或大鼠常用模型饲料


在载脂蛋白E(apolipoprotein E, ApoE)敲除的小鼠或大鼠,除非研究特殊,一般采用以下两类模型饲料之一:

♥ 高脂高胆固醇模型饲料;

♥ 高胆固醇饲料。

至于选择以上哪一种造模饲料,取决于研究目的和需要。

如果希望研究的是高脂肪高胆固醇饮食与动脉粥样硬化的关系,或者,研究的是实验干预(如,药物或食品功能因子)对动脉粥样硬化形成或发展的预防或治疗作用涉及饮食脂肪和胆固醇,则应该考虑高脂肪高胆固醇模型饲料。

如果希望研究的是饮食胆固醇与动脉粥样硬化的关系,或者,希望建立的饮食胆固醇所致的动脉粥样硬化,则选择高胆固醇饲料。

二、ApoE敲除小鼠或大鼠的年龄和造模时间


采用的ApoE敲除动物的年龄不限,取决于研究目的和需要。但要注意以下方面:

(1)要与临床相结合。虽然可以从幼年期开始进行造模,但是,要考虑到临床病人动脉粥样硬化发生的年龄,从而根据动物相应的年龄开始造模。一般文献中采用6-8周龄。

(2)要与动物机能的状态相结合。ApoE敲除鼠不仅自发发生动脉粥样硬化,而且免疫系统以及皮肤等部位异常,超过15月龄已经有很高的死亡率。因此,如果研究老龄与动脉粥样硬化的关系,或者观察动脉粥样硬化随着年龄发生改变的关系,或者研究动脉粥样硬化与老龄痴呆(AD),15个月龄是上限。

三、购买ApoE小鼠或大鼠和喂养饲料注意事项


无论是批次购买,还是引种自繁育,都应当注意对基因敲除进行确认性检测。这是使用基因工程动物的常规和必备的工作。

ApoE敲除动物的喂养与普通大小鼠的喂养相同,但是,饲料质量非常关键,一般大小鼠饲料日粮中含有大量影响动物机能的因素,因此不是理想的喂养饲料。建议采用南通特洛菲饲料科技有限公司LAD0011号饲料。

四、注意ApoE敲除的大鼠和小鼠的区别


虽然都是敲除ApoE,但是,其母本差别往往较大。在小鼠,常用的是C57BL/6小鼠为母本进行ApoE敲除,而大鼠一般是在SD大鼠上进行。由于C57BL/6小鼠是一种对脂质代谢有较高敏感的肥胖倾向的小鼠,与SD大鼠有较大的区别。一般来说,由于ApoE基因敲除大鼠的寿命短,不主张采用高脂模型饲料长期喂养的方法进行造模。

References:

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Kim MJ, Moon MK, Kang GH, Lee KJ, Choi SH, Lim S, Oh BC, Park DJ, Park KS, Jang HC, Park YJ. Chronic Exposure to Bisphenol A can Accelerate Atherosclerosis in High-Fat-Fed Apolipoprotein E Knockout Mice. Cardiovasc Toxicol. 2013 Nov 14.

Simsekyilmaz S, Cabrera-Fuentes HA, Meiler S, Kostin S, Baumer Y, Liehn EA, Weber C, Boisvert WA, Preissner KT, Zernecke A. Role of extracellular RNA in atherosclerotic plaque formation in mice. Circulation. 2014 Feb 4;129(5):598-606.

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Lu T, Wen S, Cui Y, Ju SH, Li KC, Teng GJ. Near-infrared fluorescence imaging of murine atherosclerosis using an oxidized low density lipoprotein-targeted fluorochrome. Int J Cardiovasc Imaging. 2014 Jan;30(1):221-31.

Wu X, Balu N, Li W, Chen Y, Shi X, Kummitha CM, Yu X, Yuan C, Lu ZR. Molecular MRI of atherosclerotic plaque progression in an ApoE(-/-) mouse model with a CLT1 peptide targeted macrocyclic Gd(III) chelate. Am J Nucl Med Mol Imaging. 2013 Sep 19;3(5):446-55.

Hurt-Camejo E, Gautier T, Rosengren B, Dikkers A, Behrendt M, Grass DS, Rader DJ, Tietge UJ. Expression of type IIA secretory phospholipase A2 inhibits cholesteryl ester transfer protein activity in transgenic mice. Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2707-14.

Bigalke B, Phinikaridou A, Andia ME, Cooper MS, Schuster A, Schönberger T, Griessinger CM, Wurster T, Onthank D, Ungerer M, Gawaz M, Nagel E, Botnar RM. Positron emission tomography/computed tomographic and magnetic resonance imaging in a murine model of progressive atherosclerosis using (64)Cu-labeled glycoprotein VI-Fc. Circ Cardiovasc Imaging. 2013 Nov;6(6):957-64.

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Kawahito H, Yamada H, Irie D, Kato T, Akakabe Y, Kishida S, Takata H, Wakana N, Ogata T, Ikeda K, Ueyama T, Matoba S, Mori Y, Matsubara H. Periaortic adipose tissue-specific activation of the renin-angiotensin system contributes to atherosclerosis development in uninephrectomized apoE-/- mice. Am J Physiol Heart Circ Physiol. 2013 Sep 1;305(5):H667-75.

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Zhang Y, Li L, You J, Cao J, Fu X. Effect of 7-difluoromethyl-5, 4'-dimethoxygenistein on aorta atherosclerosis in hyperlipidemia ApoE(-/-) mice induced by a cholesterol-rich diet. Drug Des Devel Ther. 2013 Apr 3;7:233-42.

Richez C, Richards RJ, Duffau P, Weitzner Z, Andry CD, Rifkin IR, Aprahamian T. The effect of mycophenolate mofetil on disease development in the gld.apoE (-/-) mouse model of accelerated atherosclerosis and systemic lupus erythematosus. PLoS One. 2013;8(4):e61042.

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Burris RL, Ng HP, Nagarajan S. Soy protein inhibits inflammation-induced VCAM-1 and inflammatory cytokine induction by inhibiting the NF-κB and AKT signaling pathway in apolipoprotein E-deficient mice. Eur J Nutr. 2014 Feb;53(1):135-48.

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Huang Q, Qin L, Dai S, Zhang H, Pasula S, Zhou H, Chen H, Min W. AIP1 suppresses atherosclerosis by limiting hyperlipidemia-induced inflammation and vascular endothelial dysfunction. Arterioscler Thromb Vasc Biol. 2013 Apr;33(4):795-804.

Cuerrier CM, Chen YX, Tremblay D, Rayner K, McNulty M, Zhao X, Kennedy CR, de BelleRoche J, Pelling AE, O'Brien ER. Chronic over-expression of heat shock protein 27 attenuates atherogenesis and enhances plaque remodeling: a combined histological and mechanical assessment of aortic lesions. PLoS One. 2013;8(2):e55867.

Ruotsalainen AK, Inkala M, Partanen ME, Lappalainen JP, Kansanen E, Mäkinen PI, Heinonen SE, Laitinen HM, Heikkilä J, Vatanen T, Hörkkö S, Yamamoto M, Ylä-Herttuala S, Jauhiainen M, Levonen AL. The absence of macrophage Nrf2 promotes early atherogenesis. Cardiovasc Res. 2013 Apr 1;98(1):107-15.

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Liu C, Desikan R, Ying Z, Gushchina L, Kampfrath T, Deiuliis J, Wang A, Xu X, Zhong J, Rao X, Sun Q, Maiseyeu A, Parthasarathy S, Rajagopalan S. Effects of a novel pharmacologic inhibitor of myeloperoxidase in a mouse atherosclerosis model. PLoS One. 2012;7(12):e50767.

Campbell IC, Weiss D, Suever JD, Virmani R, Veneziani A, Vito RP, Oshinski JN, Taylor WR. Biomechanical modeling and morphology analysis indicates plaque rupture due to mechanical failure unlikely in atherosclerosis-prone mice. Am J Physiol Heart Circ Physiol. 2013 Feb 1;304(3):H473-86.

Wan W, Lionakis MS, Liu Q, Roffê E, Murphy PM. Genetic deletion of chemokine receptor Ccr7 exacerbates atherogenesis in ApoE-deficient mice. Cardiovasc Res. 2013 Mar 1;97(3):580-8.

Boldt HB, Bale LK, Resch ZT, Oxvig C, Overgaard MT, Conover CA. Effects of mutated pregnancy-associated plasma protein-a on atherosclerotic lesion development in mice. Endocrinology. 2013 Jan;154(1):246-52.

McCarthy C, Duffy MM, Mooney D, James WG, Griffin MD, Fitzgerald DJ, Belton O. IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis. FASEB J. 2013 Feb;27(2):499-510.

Merino H, Parthasarathy S, Singla DK. Partial ligation-induced carotid artery occlusion induces leukocyte recruitment and lipid accumulation--a shear stress model of atherosclerosis. Mol Cell Biochem. 2013 Jan;372(1-2):267-73.

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ApoE基因敲除小鼠其他疾病模型复制与模型饲料

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