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药物对Caco-2单细胞层穿透性的QSPR研究
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作者 胡桂香 张长会 +1 位作者 赵文娜 俞庆森 《浙江大学学报(理学版)》 CAS CSCD 北大核心 2009年第3期304-308,共5页
Caco-2单细胞层用于模拟或预测体内小肠吸收均较剥离的小肠膜效果好.利用偏最小二乘分析方法研究VolSurf参数与药物透过Caco-2单细胞层的渗透系数之间的定量结构-性质关系(QSPR),得到较好的结果(r2=0.95,q2=0.75).对其它类药物的预测结... Caco-2单细胞层用于模拟或预测体内小肠吸收均较剥离的小肠膜效果好.利用偏最小二乘分析方法研究VolSurf参数与药物透过Caco-2单细胞层的渗透系数之间的定量结构-性质关系(QSPR),得到较好的结果(r2=0.95,q2=0.75).对其它类药物的预测结果表明,用结构不同的化合物所建立的模型对肽类药物以及同系物分子均有一定的预测能力,但是当分子的柔性键多,可能形成分子内氢键时,模型的预测能力大大下降.参数分析表明对Caco-2单细胞层渗透性高的药物分子必须具有合适的氢键给体和受体;分子内局部能量极小值越大,对渗透越有利;在一定范围内体积大且球形性高的分子对渗透有利. 展开更多
关键词 Caco-2单细胞层 VOLSURF 偏最小二乘分析(PLS) QSPR
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人结肠腺癌细胞系Caco-2单细胞层短期培养法及其评价 被引量:3
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作者 祝欣刚 杨青 《复旦学报(医学版)》 CAS CSCD 北大核心 2012年第1期68-73,共6页
目的利用丁酸建立一种短期培养人结肠腺癌细胞系Caco-2(human colon adenocarcinoma cell line)单细胞层的方法。方法使用不同成分的含丁酸培养基培养Caco-2单细胞层,通过显微镜观察细胞形态学特点、测定跨膜电阻(transepithelial elect... 目的利用丁酸建立一种短期培养人结肠腺癌细胞系Caco-2(human colon adenocarcinoma cell line)单细胞层的方法。方法使用不同成分的含丁酸培养基培养Caco-2单细胞层,通过显微镜观察细胞形态学特点、测定跨膜电阻(transepithelial electrical resistance,TEER)和荧光黄通透量等指标,评价其完整性;通过检测碱性磷酸酶(alkaline phosphatase,AKP)活性,评价其细胞极化程度;通过RT-PCR评价其对主要药物转运蛋白表达的影响。结果使用短期培养法获得的Caco-2单细胞层形态完整,TEER>500Ω.cm2,漏出标志物荧光黄表观分配系数(apparent permeability,Papp)<5×10-5 cm/s,表明单细胞层的完整性良好。同时肠腔侧(apical,AP)AKP活性显著升高,表明单细胞层出现明显的极性分化。短期培养与21天培养所得的Caco-2单细胞层中,药物转运蛋白P-糖蛋白(P-glycoprotein,P-gp)和多药耐药相关蛋白2(multidrug resistance-associated protein 2,MRP2)的RNA表达水平基本一致。结论含丁酸的无血清培养基可促进Caco-2单细胞层的快速形成,利用该法建立的Caco-2细胞模型符合各项指标的要求,可用于研究口服药物转运的吸收机制。 展开更多
关键词 CACO-2 单细胞层 短期培养 丁酸 药物转运 分化
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人参皂苷Rb_3在Caco-2单细胞层模型上的吸收特征研究 被引量:5
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作者 赵洁 杨彩华 +1 位作者 胡明 刘中秋 《中国药房》 CAS CSCD 北大核心 2010年第3期196-198,共3页
目的:研究人参皂苷Rb3在Caco-2单细胞层模型上的吸收特征。方法:人参皂苷Rb3细胞样品经高速离心后取上清液,以乙腈-1mmo·lL-1甲酸铵水溶液(34∶66)为流动相,以人参皂苷Rg2为内标,采用电喷雾离子源(ESI),在负离子条件下以多重离子... 目的:研究人参皂苷Rb3在Caco-2单细胞层模型上的吸收特征。方法:人参皂苷Rb3细胞样品经高速离心后取上清液,以乙腈-1mmo·lL-1甲酸铵水溶液(34∶66)为流动相,以人参皂苷Rg2为内标,采用电喷雾离子源(ESI),在负离子条件下以多重离子反应监测模式(MRM)检测。检测离子:m/z1077.7→m/z783.4(人参皂苷Rb3),m/z783.6→m/z475.1(人参皂苷Rg2)。测定透过Caco-2单细胞层的人参皂苷Rb3浓度并计算其表观渗透系数(Papp)。结果:人参皂苷Rb3的线性范围为50~2000ng·mL-1,日间、日内精密度均小于15%。Papp从基顶侧(AP)到基底侧(BL)为3.22×10-6cm·s-1,从BL侧到AP侧为6.0×10-6cm·s-1,其P(BL-AP)/P(AP-BL)比值为1.86。结论:本方法简单、灵敏度高,可用于研究人参皂苷Rb3在Caco-2单细胞层模型上的吸收特征。 展开更多
关键词 人参皂苷RB3 液相色谱串联质谱电喷雾法 Caco-2单细胞层模型 吸收
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UPLC法检测染料木黄酮在Caco-2单细胞层模型上的吸收特征 被引量:2
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作者 刘薇 杨珂 +2 位作者 王一飞 胡明 刘中秋 《药物评价研究》 CAS 2013年第2期127-131,共5页
目的研究染料木黄酮在Caco-2单细胞层模型上的吸收特征。方法将染料木黄酮的细胞样品经高速离心后取上清液,以乙腈-醋酸铵水溶液为流动相,以睾丸酮为内标,采用超高效液相色谱(ultra performance liquid chromatography,UPLC)法检测。考... 目的研究染料木黄酮在Caco-2单细胞层模型上的吸收特征。方法将染料木黄酮的细胞样品经高速离心后取上清液,以乙腈-醋酸铵水溶液为流动相,以睾丸酮为内标,采用超高效液相色谱(ultra performance liquid chromatography,UPLC)法检测。考察时间、pH值等因素对染料木黄酮吸收的影响,测定透过Caco-2单细胞层的染料木黄酮浓度并计算其表观渗透系数(Papp)。结果 Caco-2细胞对染料木黄酮的吸收在1 h内呈线性,药物摄取时间定为1 h;pH值对染料木黄酮的吸收没有显著影响。染料木黄酮的线性范围为0.625~40μmol/L,日间、日内精密度均小于15%。Papp从基顶侧(apical,AP)到基底侧(basolateral,BL)为1.51×10 5cm/s,从BL侧到AP侧为1.84×10 5cm/s,其渗透系数Papp(BL-AP)/Papp(AP-BL)为1.22。结论染料木黄酮在肠道的吸收主要以被动扩散为主,UPLC检测方法简单、灵敏度高,可用于研究染料木黄酮在Caco-2单细胞层模型上的吸收特征。 展开更多
关键词 染料木黄酮 超高效液相色谱 Caco-2单细胞层模型 吸收
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Caco-2细胞模型在口服药物吸收研究中的应用 被引量:38
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作者 高坤 孙进 何仲贵 《沈阳药科大学学报》 CAS CSCD 北大核心 2005年第6期469-474,共6页
目的对Caco-2细胞模型在口服药物肠吸收研究中的应用作一综述.方法在引用了自1974~2004年的32篇文献的基础上,通过介绍并比较体外Caco-2模型和体内药物吸收转运的不同途径,讨论Caco-2单层细胞模型在预测不同类药物体内吸收中的作用.结... 目的对Caco-2细胞模型在口服药物肠吸收研究中的应用作一综述.方法在引用了自1974~2004年的32篇文献的基础上,通过介绍并比较体外Caco-2模型和体内药物吸收转运的不同途径,讨论Caco-2单层细胞模型在预测不同类药物体内吸收中的作用.结果 Caco-2细胞模型可以预测不同转运途径的药物体内吸收,尤其适用于被动转运药物,这一细胞模型在药物吸收机制、处方组成透膜性和黏膜毒性、药物吸收过程中的相互作用、药物的化学结构和体内转运关系、药物吸收限速因素、药物代谢稳定性及pH对药物吸收的影响等研究中均有较广泛的应用.结论 Caco-2细胞模型用于预测各种途径的药物吸收,在细胞水平上提供了大量与吸收相关的信息,是口服药物高通量筛选的良好工具. 展开更多
关键词 药物转运 药物吸收 CACO-2 单细胞层
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血管内皮通透性调节机制新进展 被引量:5
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作者 张庆芝 闵锐 《中国微循环》 2009年第6期585-588,共4页
关键词 血管内皮通透性 调节 周围组织 血管内皮细胞 物质运输 单细胞层 内皮损伤 细胞
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我国科学家首次详尽揭示肝癌免疫图谱
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《肿瘤防治研究》 CAS CSCD 北大核心 2017年第7期514-514,共1页
近日,我国科学家对取自多个肝癌患者的5000余个T细胞逐个进行了基因测序,从而勾勒出每个细胞的基因表达图谱,这是世界上首次对癌症患者体内的T细胞在单细胞层面上进行如此大规模的详尽分析,为未来发现肝痛及其他癌症的免疫疗法奠定... 近日,我国科学家对取自多个肝癌患者的5000余个T细胞逐个进行了基因测序,从而勾勒出每个细胞的基因表达图谱,这是世界上首次对癌症患者体内的T细胞在单细胞层面上进行如此大规模的详尽分析,为未来发现肝痛及其他癌症的免疫疗法奠定了基础。 展开更多
关键词 基因表达图谱 肝癌患者 免疫疗法 科学家 癌症患者 T细胞 基因测序 单细胞层
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Upregulated CD133 expression in tumorigenesis of colon cancer cells 被引量:9
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作者 Zhi-Li Yang Qi Zheng Jun Yan Ye Pan Zhi-Gang Wang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第7期932-937,共6页
AIM: To analyze the upregulated CD133 expression in tumorigenesis of primary colon cancer cells. METHODS: Upregulated CD133 expression in tumorigenesis of colorectal cancer cell lines (Lovo, Colo205, Caco-2, HCT116 an... AIM: To analyze the upregulated CD133 expression in tumorigenesis of primary colon cancer cells. METHODS: Upregulated CD133 expression in tumorigenesis of colorectal cancer cell lines (Lovo, Colo205, Caco-2, HCT116 and SW620) was analyzed by flow cytometry. Human colon cancer tissue samples were stained with anti-human CD133. SW620 cells were sorted according to the CD133 expression level measured by fluorescence-activated cell sorting. Spheroids of colorectal cancer cells were cultured with the hanging drop. Expression of CD133 and Lgr5 in spheroids of colorectal cancer cells and monolayer culture was detected by RT-qPCR. Spheroids of colorectal cancer cells were analyzed using anti-human CD133 with immunohistochemical staining. RESULTS: CD133 antigen was expressed in colorectal cancer cell lines (Lovo, Colo205, Caco-2, HCT116 and SW620) as well as in primary and metastatic human colon cancer tissues. However, the CD133 was differently expressed in these cell lines and tissues. The expression levels of CD133 and Lgr5 were significantly higher in spheroids of parental, CD133hi and CD133-cells than in their monolayer culture at the mRNA level (P < 0.05). Immunohistochemical staining of spheroids of CD133-cells showed that CD133 was highly expressed in colorectal cancer cell lines. CONCLUSION: Upregulated CD133 expression plays a role in tumorigenesis colorectal cancer cells, which may promote the expression of other critical genes that can drive tumorigenesis. 展开更多
关键词 CD133 Colon cancer cells TUMORIGENESIS Cancer stem cells
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Influence of Cell Components Structure on Heat and Mass Transfer Phenomena in Single-Cell PEFC
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作者 Akira Nishimura Atsushi Morimoto +5 位作者 Shigeki Tanaka Atsushi Oshima Masafumi Hirota Eiji Tohma Yukio Kimura Masahiko Narita 《Journal of Energy and Power Engineering》 2012年第4期504-518,共15页
The purpose of this study is to point out the dominant factor of heat and mass distribution in single-cell PEFC (polymer electrolyte fuel cell). The numerical simulation by simple 3D model to clarify the influence o... The purpose of this study is to point out the dominant factor of heat and mass distribution in single-cell PEFC (polymer electrolyte fuel cell). The numerical simulation by simple 3D model to clarify the influence of cell components structure on heat and mass transfer phenomena as well as power generation experiment and measurement of in-plane temperature distribution by thermograph was carried out. From the simulation, the gas channel pitch of separator was the key factor to unify in-plane distribution of temperature and gas concentration on reaction surface in cell. The compression of GDL (gas diffusion layer) by cell binding caused wider distribution of mass concentration in GDL. From the experiment, the power generation performance was promoted with decreasing gas channel pitch. The temperature range in observation area was reduced with decreasing gas channel pitch. It can be concluded that the power generation performance is promoted by decreasing gas channel pitch. 展开更多
关键词 PEFC gas channel pitch effect of compression of GDL heat and mass transfer.
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Intestinal permeability of liquiritin and isoliquiritin in the Caco-2 cell monolayer model 被引量:3
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作者 张力勤 黄应栋 杨秀伟 《Journal of Chinese Pharmaceutical Sciences》 CAS 2010年第6期451-458,共8页
The intestinal permeability of two flavonoid compounds liquiritin (LQ) and isoliquiritin (ILQ) was investigated using the Caco-2 cell monolayer model. In order to evaluate the permeability and predict the absorpti... The intestinal permeability of two flavonoid compounds liquiritin (LQ) and isoliquiritin (ILQ) was investigated using the Caco-2 cell monolayer model. In order to evaluate the permeability and predict the absorption mechanism of the two compounds, the study on bidirectional permeability from the apical (AP) side to the basolateral (BL) side as well as from the BL side to the AP side was carried out. The determination was performed by HPLC-UV method. And the permeability parameters, especially the apparent permeability coefficients (Papp), were then calculated. The Papp values of LQ and ILQ are (5.40±0.16)× 10^-7 and (8.69±0.15)× 10^-7 cm/s, respectively. The results of time- and concentration-dependent transport experiments indicate that both LQ and ILQ are poor absorbed mainly through passive diffusion. 展开更多
关键词 LIQUIRITIN ISOLIQUIRITIN Caco-2 cell monolayer model Intestinal permeability
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Intestinal permeability of atractylenolides across the human Caco-2 cell monolayer model 被引量:1
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作者 郭洁 徐嵬 杨秀伟 《Journal of Chinese Pharmaceutical Sciences》 CAS 2011年第5期505-509,共5页
The intestinal permeability of three sesquiterpene lactones, atractylenolide Ⅰ, Ⅱ, and Ⅲ, was investigated using the human Caco-2 cell monolayer model. The bidirectional permeability of the three compounds from the... The intestinal permeability of three sesquiterpene lactones, atractylenolide Ⅰ, Ⅱ, and Ⅲ, was investigated using the human Caco-2 cell monolayer model. The bidirectional permeability of the three compounds from the apical (AP) to the basolateral (BL) side and in the reserved direction was studied. The three compounds were assayed using HPLC. The Papp values of atractylenolide Ⅰ, Ⅱ, and Ⅲ were all at the level of 10^-5 cm/s, suggesting high intestinal permeability and good absorption. The bidirectional transport of the three compounds was time- and concentration-dependent, and indicated the main mechanism of the passive diffusion of the three compounds across the intestinal epithelium membrane. Moreover, atractylenolide Ⅰ might be partly actively transported. 展开更多
关键词 Atractylenolide Atractylenolide Atractylenolide Caco-2 cell monolayer model Intestinal permeability
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The blood-brain barrier permeability of 20(S) and 20(R)-protopanaxatriol epimers and dammar-20(22)E,24-diene-3β,6α,12β-triol in MDCK-pHa MDR cell monolayer model 被引量:1
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作者 郑怡然 吴秀稳 杨秀伟 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2017年第8期566-573,共8页
The blood-brain barrier permeability of 20(S) and 20(R)-protopanaxatriol epimers and dammar-20(22)E,24-diene- 313,6α,12β-triol were investigated using the MDCK-pHaMDR cell monolayer model. The bidirectional pe... The blood-brain barrier permeability of 20(S) and 20(R)-protopanaxatriol epimers and dammar-20(22)E,24-diene- 313,6α,12β-triol were investigated using the MDCK-pHaMDR cell monolayer model. The bidirectional permeability tests were carried out, and the apparent permeability coefficients (Papp) were calculated. The two protopanaxatriol epimers showed good permeability with Papp values of-10^-5 cm/s, whereas dammar-20(22)E,24-diene-3β,6α, 12β-triol showed poor permeability with Papp of 〈1 × 10^-7 cm/s. The three compounds showed differences in intracellular accumulations due to their different structures. Inhibition of P-gp with verapamil showed that the transport mechanisms in MDCK-pHaMDR cell monolayer for compounds 1 and 2 epimers were not only simple passive diffusion but also involving an effiux way mediated by P-gp. These findings provided new basis for the further study of compounds 1 and 2 acting on the brain. 展开更多
关键词 20(S)-Protopanaxatriol 20(R)-Protopanaxatriol Dammar-20(22)E 24-diene-3β 12β-triol MDCK-pHaMDR Permeability Blood-brain barrier
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