微囊流化培养对C3A细胞功能的影响及其机制研究  

Study of the effect of microcapsule fluidized culture on C3A cell function and its molecular mechanism

作　　者：李晓青[1] 李建州 杨英[3] 李兰娟[3] LI Xiaoqing;LI Jianzhou;YANG Ying;LI Lanjuan(Department of Emergency,First Affiliated Hospital of Xi’an JiaoTong University,Shaanxi Province,Xi’an 710061,China;Department of Infectious Diseases,First Affiliated Hospital of Xi’an JiaoTong University,Shaanxi Province,Xi’an 710061,China;State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,Zhejiang Province,Hangzhou 310003,China)

机构地区：[1]西安交通大学第一附属医院急诊科,陕西西安710061 [2]西安交通大学第一附属医院感染科,陕西西安710061 [3]浙江大学传染病诊治国家重点实验室,浙江杭州310003

出　　处：《中国医药导报》2021年第15期4-8,26,共6页China Medical Herald

基　　金：十三五国家科技重大专项(2017ZX10203201);国家自然科学基金资助项目(81700559)。

摘　　要：目的探讨微囊流化培养对C3A细胞功能的影响及其机制。方法根据C3A细胞培养模式的不同将其分为三组,二维培养组、微囊静态培养组和微囊流化培养组。评估微囊流化培养对C3A细胞活性的影响,比较不同培养模式对C3A细胞白蛋白、尿素合成能力及代谢能力的影响,检测肝细胞功能相关基因的表达水平,检测肝细胞代谢相关信号通路关键分子的表达水平。结果微囊静态及微囊流化培养组C3A细胞的白蛋白、尿素合成能力和CYP1A2、CYP3A4代谢活性高于二维培养组,差异有统计学意义(P<0.05)。与微囊静态培养组比较,微囊流化培养组C3A细胞的白蛋白、尿素合成能力及CYP1A2代谢活性升高,差异有统计学意义(P<0.05)。微囊静态及微囊流化培养组C3A细胞的CYP1A2、CYP2B62、CYP2E1、CYP3A4、UGT2B4基因的表达水平高于二维培养组,差异有统计学意义(P<0.05)。与微囊静态培养组比较,微囊流化培养组C3A细胞代谢相关信号通路p-PKC、p-PKA、钙调蛋白(CaM)的表达水平降低,差异有统计学意义(P<0.05)。结论微囊流化培养能够显著提高C3A细胞的合成及代谢能力,其作用机制可能与下调相关信号通路的磷酸化及CaM的水平有关。Objective To investigate the effect of microcapsule fluidized culture on C3A cell function and its molecular mechanism.Methods Base on the different culture modes of C3A cells,they were divided into three groups:two-dimensional culture group,microcapsule static culture group and microcapsule fluidized culture group.The effect of microencapsulation fluidized culture on the activity of C3A cells,albumin,urea synthesis capacity and metabolism ability was evaluated.The expression level of genes related to hepatocyte function was detected.The expression levels of key molecules in metabolism-related signaling pathways of hepatocytes were detected.Results The albumin,urea synthesis capacity and CYP1A2,CYP3A4 metabolic activity of C3A cells in the microcapsule static culture group and microencapsulation fluidized culture group were higher than those in the two-dimensional culture group,and the differences were statistically significant(P<0.05).Compared with the microcapsule static culture group,the albumin,urea synthesis capacity and CYP1A2 metabolic activity of C3A cells in the microcapsule fluidized culture group were increased,and the differences were statistically significant(P<0.05).The expression levels of CYP1A2,CYP2B62,CYP2E1,CYP3A4 and UGT2B4 genes of C3A cells in the microcapsule static culture group and microencapsulation fluidized culture group were higher than those in the two-dimensional culture group,and the differences were statistically significant(P<0.05).Compared with the microcapsule static culture group,the expression levels of p-PKC,p-PKA and calmodulin(CaM)proteins related to metabolism of C3A cells in the microcapsule fluidized culture group were decreased,and the differences were statistically significant(P<0.05).Conclusion Microcapsule fluidized culture can significantly improve the synthesis and metabolism fuction of C3A cells,and its mechanism of action may be related to the down-regulation of the phosphorylation level of related signaling pathway proteins and level of CaM.

关 键 词：肝衰竭 生物人工肝 微囊 肝细胞 流化床式反应器 

分 类 号：R318.1[医药卫生—生物医学工程]