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Caco-2细胞

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Caco-2细胞

Caco-2人类结肠腺癌细胞系,最初是在1977年纪念斯隆-凯特琳癌症中心研究员从一名72岁的白人男性结肠腺癌患者分离出来。

特征

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Caco-2细胞拥有与小肠上皮细胞刷状缘英语Brush border相关的酶系英语Cyclic enzyme system[1][2],而且其结构、标志酶的特异性表达与渗透性等方面均与人类小肠上皮细胞相近[3]。在体外培养Caco-2细胞的过程中,会发现生长在多孔膜上的Caco-2细胞会形成朝向上皮样分化单细胞层英语Monolayer。Caco-2细胞具有微绒毛结构,并且与相邻的细胞紧密地结合,同时又会分泌水解酶,以及合成氨基酸等的载体转运系统[1]

科研用途

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Caco-2细胞在遗传学等方面均是最令人满意的上皮细胞系[4],所以Caco-2细胞构建的模型,不仅是吸收营养素毒素效果最良好的体外模型,还可以模拟小肠上皮细胞吸收、代谢及转运口服药物与营养物质分子等的过程[5][6]。这可以预测不同转运途径的食物营养物质在体内的吸收、营养物质的化学结构和体内转运关系、营养物质代谢稳定性氢离子浓度指数对营养物质吸收的影响等[7]。因此,Caco-2细胞广泛应用于开发新型药物、研究肠内药物吸收英语Absorption (pharmacology)机制等,甚至被应用在叶酸吸收与红血球生成素作用的研究[8][9]

营养方面的部分研究
研究 描述 资料来源
植物凝集素对食物因子的运输作用 研究发现其会增加离子异黄酮的运输,但是不会影响糖苷配基及鹅肌肽等的运输,并且表明其对Caco-2细胞紧密连接的作用较微弱。 [10]
卵黄高磷蛋白磷酸肽对过氧化氢的保护作用 研究发现其会抑制Caco-2细胞 (细胞已被过氧化氢处理) 中体内氧化应激标志物丙二醛的生成。 [11]
Caco-2细胞对水溶性秀珍菇多糖抗氧化剂的调控机制 研究发现其能抑制消化道中结肠癌对Caco-2细胞无细胞基底膜的入侵。 [12]
对Caco-2细胞紧密连接性及通透性的影响 有研究发现壳聚糖、聚阳离子及多聚赖氨酸都能增强细胞的紧密连接性及通透性,前两者受浓度的影响,后者受分子量的影响,或会令细胞黏膜出现变化。 [13]
蓝莓花青素提取物的吸收情况 花青素是以完整糖醛形式通过Caco-2细胞,但是转运吸收效率因水溶性花色素苷亲脂性差而低于部分苷元多酚 [14]
膳食多酚对摄取葡萄糖的影响 研究发现糖苷配基抑制着Caco-2细胞摄取葡萄糖,而糖苷则抑制着葡萄糖的转运。钙离子存在时,有利于细胞通过钠依赖型葡萄糖共同运输蛋白-1英语Sodium/glucose cotransporter 1 (一种次级葡萄糖载体蛋白) 摄取葡萄糖。钙离子不存在时,则有利于细胞通过葡萄糖载体蛋白英语Glucose transporter摄取葡萄糖。 [15]
类胡萝卜素的吸收情况 研究发现Caco-2细胞摄取的胡萝卜素玉米黄素均高于叶黄素 [16]
对细胞中胆固醇吸收的影响 研究发现经毛地黄黄酮五羟黄酮处理的Caco-2细胞,其胆固醇摄取明显地降低。 [17]
异黄酮的摄取和代谢情况 研究发现异黄酮比大豆苷更有效地转运至Caco-2细胞,表明异黄酮糖苷配基因具有一定的亲脂性而较葡萄糖苷有效摄入至肠细胞。 [18]
黄芩苷及黄芩素细胞中的吸收和排泄 研究发现黄芩素被葡萄糖醛酸化英语Glucuronidation成黄芩苷,进而通过多药耐药相关蛋白2英语Multidrug resistance-associated protein 2等的外排作用,从顶端表面排泄出来。 [19]

衍生细胞系

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参考资料

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  1. ^ 1.0 1.1 Hidalgo, IJ; Raub, TJ; Borchardt, RT. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability.. Gastroenterology. 1989-03, 96 (3): 736–49 [2019-12-17]. PMID 2914637. (原始内容存档于2019-12-17). 
  2. ^ Hubatsch, I; Ragnarsson, EG; Artursson, P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers.. Nature protocols. 2007, 2 (9): 2111–9 [2019-12-17]. PMID 17853866. doi:10.1038/nprot.2007.303. (原始内容存档于2019-12-17). 
  3. ^ Jobbágyi, P; Heszberger, I. [Local cryotechnique and prevention of freezing injuries].. Klinische Monatsblatter fur Augenheilkunde. 1966, 149 (2): 246–51 [2019-12-17]. PMID 5986493. 
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  6. ^ Artursson, P; Palm, K; Luthman, K. Caco-2 monolayers in experimental and theoretical predictions of drug transport.. Advanced drug delivery reviews. 2001-03-01, 46 (1-3): 27–43 [2019-12-17]. PMID 11259831. doi:10.1016/s0169-409x(00)00128-9. (原始内容存档于2019-12-17). 
  7. ^ Tavelin, S; Gråsjö, J; Taipalensuu, J; Ocklind, G; Artursson, P. Applications of epithelial cell culture in studies of drug transport.. Methods in molecular biology (Clifton, N.J.). 2002, 188: 233–72 [2019-12-17]. PMID 11987548. doi:10.1385/1-59259-185-X:233. (原始内容存档于2019-12-17). 
  8. ^ Ashokkumar, B; Mohammed, ZM; Vaziri, ND; Said, HM. Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells.. The American journal of clinical nutrition. 2007-07, 86 (1): 159–66 [2019-12-17]. PMID 17616776. doi:10.1093/ajcn/86.1.159. (原始内容存档于2019-12-17). 
  9. ^ Verwei, M; van den Berg, H; Havenaar, R; Groten, JP. Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells.. European journal of nutrition. 2005-06, 44 (4): 242–9 [2019-12-17]. PMID 15316828. doi:10.1007/s00394-004-0516-9. (原始内容存档于2019-12-17). 
  10. ^ Ohno, Y; Naganuma, T; Ogawa, T; Muramoto, K. Effect of lectins on the transport of food factors in caco-2 cell monolayers.. Journal of agricultural and food chemistry. 2006-01-25, 54 (2): 548–53 [2019-12-22]. PMID 16417319. doi:10.1021/jf052040y. (原始内容存档于2019-12-22). 
  11. ^ Katayama, S; Xu, X; Fan, MZ; Mine, Y. Antioxidative stress activity of oligophosphopeptides derived from hen egg yolk phosvitin in Caco-2 cells.. Journal of agricultural and food chemistry. 2006-02-08, 54 (3): 773–8 [2019-12-22]. PMID 16448181. doi:10.1021/jf052280d. (原始内容存档于2019-12-22). 
  12. ^ Soler-Rivas, Cristina; Ramírez-Anguiano, Ana Cristina; Reglero, Guillermo; Santoyo, Susana. Effect of cooking, digestion and Caco-2 cells absorption on the radical scavenging activities of edible mushrooms. International Journal of Food Science & Technology. 2009-11, 44 (11): 2189–2197. doi:10.1111/j.1365-2621.2009.02059.x. 
  13. ^ Ranaldi, G; Marigliano, I; Vespignani, I; Perozzi, G; Sambuy, Y. The effect of chitosan and other polycations on tight junction permeability in the human intestinal Caco-2 cell line(1).. The Journal of nutritional biochemistry. 2002-03, 13 (3): 157–167 [2019-12-22]. PMID 11893480. doi:10.1016/s0955-2863(01)00208-x. (原始内容存档于2019-12-22). 
  14. ^ Yi, W; Akoh, CC; Fischer, J; Krewer, G. Absorption of anthocyanins from blueberry extracts by caco-2 human intestinal cell monolayers.. Journal of agricultural and food chemistry. 2006-07-26, 54 (15): 5651–8 [2019-12-22]. PMID 16848559. doi:10.1021/jf0531959. (原始内容存档于2019-12-22). 
  15. ^ Johnston, K; Sharp, P; Clifford, M; Morgan, L. Dietary polyphenols decrease glucose uptake by human intestinal Caco-2 cells.. FEBS letters. 2005-03-14, 579 (7): 1653–7 [2019-12-22]. PMID 15757656. doi:10.1016/j.febslet.2004.12.099. (原始内容存档于2019-12-22). 
  16. ^ Liu, CS; Glahn, RP; Liu, RH. Assessment of carotenoid bioavailability of whole foods using a Caco-2 cell culture model coupled with an in vitro digestion.. Journal of agricultural and food chemistry. 2004-06-30, 52 (13): 4330–7 [2019-12-23]. PMID 15212488. doi:10.1021/jf040028k. (原始内容存档于2019-12-23). 
  17. ^ Nekohashi, M; Ogawa, M; Ogihara, T; Nakazawa, K; Kato, H; Misaka, T; Abe, K; Kobayashi, S. Luteolin and quercetin affect the cholesterol absorption mediated by epithelial cholesterol transporter niemann-pick c1-like 1 in caco-2 cells and rats.. PloS one. 2014, 9 (5): e97901 [2019-12-23]. PMID 24859282. doi:10.1371/journal.pone.0097901. (原始内容存档于2019-12-23). 
  18. ^ Murota, K; Shimizu, S; Miyamoto, S; Izumi, T; Obata, A; Kikuchi, M; Terao, J. Unique uptake and transport of isoflavone aglycones by human intestinal caco-2 cells: comparison of isoflavonoids and flavonoids.. The Journal of nutrition. 2002-07, 132 (7): 1956–61 [2019-12-23]. PMID 12097676. doi:10.1093/jn/132.7.1956. (原始内容存档于2019-12-23). 
  19. ^ Akao, T; Hanada, M; Sakashita, Y; Sato, K; Morita, M; Imanaka, T. Efflux of baicalin, a flavone glucuronide of Scutellariae Radix, on Caco-2 cells through multidrug resistance-associated protein 2.. The Journal of pharmacy and pharmacology. 2007-01, 59 (1): 87–93 [2019-12-23]. PMID 17227625. doi:10.1211/jpp.59.1.0012. (原始内容存档于2019-12-23). 

外部链接

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