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Clinton-Cybulsky高脂肪高胆固醇模型饲料的
特点、存在的问题与纠正
Clinton-Cybulsky Diet for Western Diet Model

Clinton-Cybulsky高脂肪高胆固醇模型饲料的种类
【1】40%脂肪、1.25%胆固醇、0.5%胆酸(胆盐)饲料。
【2】40%脂肪、1.25%胆固醇饲料。
【3】40%脂肪、0.5%胆固醇饲料。

ResearchDiets公司将这个模型饲料的名称以Clinton和Cybulsky来命名,这让我们不解。实际上,在第一次用这个模型饲料的研究者当中,第一作者和通讯作者都不是其人。

一、Clinton-Cybulsky diet


Clinton-Cybulsky模型饲料是高脂肪高胆固醇模型饲料,包括(1)含1.25%胆固醇和0.5%胆盐;(2)1.25%胆固醇、不加胆盐;(3)0.5%胆固醇、不加胆盐。目的是比较动物对不加胆盐、不同胆固醇情况下的反应。实际上,其中添加1.25%胆固醇、0.5%胆盐的模型饲料就是Paigen饲料,用于后两种模型饲料对比用的。因此,严格意义上,Clinton-Cybulsky模型饲料只是第二种和第三种模型饲料。

二、Clinton-Cybulsky diet的特点、用途和缺点


Clinton-Cybulsky高脂肪高胆固醇模型饲料的用途

广泛应用于多种动物或不同品系的高血脂模型高胆固醇血症模型胰岛素抵抗模型II型糖尿病模型代谢综合症模型非酒精性脂肪肝模型胆结石模型动脉粥样硬化模型、血管内皮细胞损伤或炎症,等等。请注意不同种系和品系的差异。

Clinton-Cybulsky模型饲料 的脂肪热量40%,胆固醇0.5%或1.25%。由于脂肪热量为40%,一方面饲料总热量不是很高,另一方面,这个饲料的脂肪水平在高脂饲料当中属于中等,并且比较符合西方饮食。此外,模型饲料中糖的含量不高,对于大鼠、小鼠等动物来说,属于可接受的水平。总的来说,Clinton-Cybulsky模型饲料属于高脂肪、高胆固醇饲料。

Clinton-Cybulsky模型饲料应用非常广泛,主要原因是,可以根据使用的动物对模型饲料的敏感程度进行选择。主要用途见右图。

然而,Clinton-Cybulsky模型饲料最初计主要是针对未成年动物的喂养,如果使用成年动物,就需要重新设计。此外,ResearchDietsg公司在最初设计该模型饲料时营养素就不合理,有关缺点见下图。

Clinton-Cybulsky高脂肪高胆固醇模型饲料的缺点
(1)营养素不合理,需要优化。
(2)饲料成分数据不准确。
(3)只适用于未成年、妊娠、哺乳期的大小鼠。成年期使用需要重新设计。

ResearchDiets、TestDiet公司和南通特洛菲饲料科技有限公司提供的Clinton-Cybulsky模型饲料的代码见下表。

不同公司Clinton-Cybulsky模型饲料代码表
公司
1.25%胆固醇,0.5%胆盐
1.25%胆固醇
0.5%胆固醇
对照饲料
说明
ResearchDiets
D12109
D12108
D12107
D12102
一直沿用,未优化
TestDiet
58R7
58R6
58R5
58R0
一直沿用,未优化
南通特洛菲
TP28540
TP28541
TP28542
TP28548, TP28549
与以上公司相同,没有优化
南通特洛菲
TP28500
TP28501
TP28502
TP28508, TP28509
优化,用于未成年,妊娠期、哺乳期)
南通特洛菲
TP28520
TP28521
TP28522
TP28528, TP28529
专门设计,用于成年

三、特洛菲饲料科技有限公司提供的Clinton-Cybulsky高脂高胆固醇模型饲料的策略


从上表看到,针对Clinton-Cybulsky高脂高胆固醇模型饲料存在的问题,特洛菲饲料科技有限公司采取了优化、不优化和重新设计三种办法让研究者选择。尤其是,重新设计的针对成年期喂养的模型饲料为研究成年动物提供了方便。


References:

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[25] Abidi P, Chen W, Kraemer FB, Li H, Liu J.The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms.J Lipid Res. 2006 Oct;47(10):2134-47.

[26] Tang EH, Shvartz E, Shimizu K, Rocha VZ, Zheng C, Fukuda D, Shi GP, Sukhova G, Libby P.Deletion of EP4 on bone marrow-derived cells enhances inflammation and angiotensin II-induced abdominal aortic aneurysm formation.Arterioscler Thromb Vasc Biol. 2011 Feb;31(2):261-9.

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[29] Zhu SN, Chen M, Jongstra-Bilen J, Cybulsky MI. GM-CSF regulates intimal cell proliferation in nascent atherosclerotic lesions.J Exp Med. 2009 Sep 28;206(10):2141-9.

[30] Packard RR, Maganto-García E, Gotsman I, Tabas I, Libby P, Lichtman AH. CD11c(+) dendritic cells maintain antigen processing, presentation capabilities, and CD4(+) T-cell priming efficacy under hypercholesterolemic conditions associated with atherosclerosis.Circ Res. 2008 Oct 24;103(9):965-73.

[31] Franco C, Hou G, Ahmad PJ, Fu EY, Koh L, Vogel WF, Bendeck MP. Discoidin domain receptor 1 (ddr1) deletion decreases atherosclerosis by accelerating matrix accumulation and reducing inflammation in low-density lipoprotein receptor-deficient mice.Circ Res. 2008 May 23;102(10):1202-11.

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[33] Gotsman I, Grabie N, Gupta R, Dacosta R, MacConmara M, Lederer J, Sukhova G, Witztum JL, Sharpe AH, Lichtman AH. Impaired regulatory T-cell response and enhanced atherosclerosis in the absence of inducible costimulatory molecule.Circulation. 2006 Nov 7;114(19):2047-55.

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[35] Paulson KE, Zhu SN, Chen M, Nurmohamed S, Jongstra-Bilen J, Cybulsky MI. Resident intimal dendritic cells accumulate lipid and contribute to the initiation of atherosclerosis.Circ Res. 2010 Feb 5;106(2):383-90.

[36] Sales VL, Sukhova GK, Lopez-Ilasaca MA, Libby P, Dzau VJ, Pratt RE. Angiotensin type 2 receptor is expressed in murine atherosclerotic lesions and modulates lesion evolution.Circulation. 2005 Nov 22;112(21):3328-36.

[37] Jacobs RL, Stead LM, Devlin C, Tabas I, Brosnan ME, Brosnan JT, Vance DE. Physiological regulation of phospholipid methylation alters plasma homocysteine in mice.J Biol Chem. 2005 Aug 5;280(31):28299-305.

[38] Soccio RE, Adams RM, Maxwell KN, Breslow JL. Differential gene regulation of StarD4 and StarD5 cholesterol transfer proteins. Activation of StarD4 by sterol regulatory element-binding protein-2 and StarD5 by endoplasmic reticulum stress. J Biol Chem. 2005 May 13;280(19):19410-8.

[39] Sukhova GK, Zhang Y, Pan JH, Wada Y, Yamamoto T, Naito M, Kodama T, Tsimikas S, Witztum JL, Lu ML, Sakara Y, Chin MT, Libby P, Shi GP. Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice.J Clin Invest. 2003 Mar;111(6):897-906.

[40] Sukhova GK, Wang B, Libby P, Pan JH, Zhang Y, Grubb A, Fang K, Chapman HA, Shi GP. Cystatin C deficiency increases elastic lamina degradation and aortic dilatation in apolipoprotein E-null mice.Circ Res. 2005 Feb 18;96(3):368-75.

[41] Buono C, Pang H, Uchida Y, Libby P, Sharpe AH, Lichtman AH. B7-1/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice.Circulation. 2004 Apr 27;109(16):2009-15.

[42] Tiemann M, Han Z, Soccio R, Bollineni J, Shefer S, Sehayek E, Breslow JL. Cholesterol feeding of mice expressing cholesterol 7alpha-hydroxylase increases bile acid pool size despite decreased enzyme activity.Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1846-51.

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[44] Maxwell KN, Soccio RE, Duncan EM, Sehayek E, Breslow JL. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice.J Lipid Res. 2003 Nov;44(11):2109-19.

[45] Buono C, Come CE, Stavrakis G, Maguire GF, Connelly PW, Lichtman AH.Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse. Arterioscler Thromb Vasc Biol. 2003 Mar 1;23(3):454-60.

[46] Buono C, Come CE, Witztum JL, Maguire GF, Connelly PW, Carroll M, Lichtman AH.Influence of C3 deficiency on atherosclerosis.Circulation. 2002 Jun 25;105(25):3025-31.

[47] Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI.The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation.Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9052-7.

[48] Abidi P, Chen W, Kraemer FB, Li H, Liu J. The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms.J Lipid Res. 2006 Oct;47(10):2134-47.

[49] Iiyama K, Hajra L, Iiyama M, Li H, DiChiara M, Medoff BD, Cybulsky MI. Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation.Circ Res. 1999 Jul 23;85(2):199-207.

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有困惑?那就商量呗!

高脂肥胖、代谢综合症、胰岛素抵抗、高血脂(高甘油三酯血症、高胆固醇血症)、糖尿病、动脉粥样硬化、非酒精性脂肪肝,等模型饲料

南通特洛菲饲料科技有限公司提供各种动物、各种类型的肥胖及其并发症的模型饲料。

---------《》-------

大鼠小鼠Clinton-Cybulsky高脂高胆固醇模型饲料(TP28500系列):

markerTP28540, TP28541, TP28542

TP28540含0.5%胆盐、1.25%胆固醇;TP28541含1.25%胆固醇;TP28542含0.5%胆固醇。

没有优化,分别与Lichtman等使用的ResearchDiets公司D12109、D12108、D12017相当,或者分别与TestDiet公司58R7、58R6、58R5相当。为追求与这些模型饲料相当的研究者设计。用于未成年、妊娠哺乳期。

markerTP28500, TP28501, TP28502

TP28500含0.5%胆盐、1.25%胆固醇;TP28501含1.25%胆固醇;TP28502含0.5%胆固醇。

营养素优化到合理水平,使研究更可靠。用于未成年、妊娠、哺乳期。

markerTP28520, TP28521, TP28522

TP28520含0.5%胆盐、1.25%胆固醇;TP28521含1.25%胆固醇;TP28522含0.5%胆固醇。

专门针对成年动物设计,用于成年期喂养。

marker不同脂肪类型

如果希望改用其他脂肪类型,可以进行修改,相应的饲料代码在《选择指南》中做了说明。




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