mdr-1基因转染的骨髓细胞对大剂量mmf治疗的耐受性研究.docVIP

Mdr-1基因转染的骨髓细胞对大剂量MMF治疗的耐受性研究 李 钺，栾晓峰，陈 勇，龚建平，陈先锋，丁 雄，刘作金 （重庆医科大学附属第二医院肝胆外科，重庆市肝胆外科重点实验室，重庆400010） 摘 要：目的 检测转染多药耐药基因-1（multidrug resistance gene-1，mdr-1）霉酚酸脂mycophenolate mofetil，MMFAd-EGFP-mdr-1转染大鼠骨髓细胞。RT-PCR法Western-blot法检测mdr1 mRNA及蛋白的表达柔红霉素排出试验检测mdr-1基因功能mdr-1基因。骨髓细胞mdr1的mRNA及蛋白质功能性表达导入的mdr1表达产物P-gp有药物外排泵功能超大剂量霉酚酸脂The effects of mdr-1 transfected bone marrow cells on overdose mycophenolate mofetil treatment LI Yue, LUAN Xiaofeng, CHENG Yong, GONG Jianping, CHENG Xianfeng, DING Xiong, LIU Zuojin (Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 4000l0, China) Abstract: Objective To investigate whether bone marrow cells (BMC) transferred with multidrug resistance gene-1 (mdr-1) could tolerate overdose mycophenolate mofetil (MMF). Methods The BMC of the Brown Norway (BN) rats were transferred with Ad-EGFP-mdr-1. RT-PCR, Western-blot and daunorubicin (DAM) methods were used to detect the functional expression of mdr1 gene; the survival rat of the transferred BMC treated by different dose MMF were measured by MTT. Results The transfection efficiency of the virus was 30.14%, and the survival rate of the BMC was 89.25%. There was obvious functional expression of the mdr-1 gene in the transferred BMC. MTT demonstrated that transferred BMC could bear different dosage of MMF, there were no obvious difference of their survival rates (P0.05). Conclusions The exogenous mdr-1 gene could be transferred into BMC efficiently in vitro, thus provide promising therapeutic modalities in vivo. Key words: Multidrug resistance gene-1; mycophenolate mofetil; bone marrow cells 目前肝移植术后采用的细胞毒性药物、神经碱钙抑制剂急性排斥反应（acute rejectionAcR）得到良好控制，但机体肿瘤免疫机能不可避免的进一步被削弱，进而成为术后肿瘤复发的重要原因。霉酚酸脂mycophenolate mofetil，MMF）是选择性的嘌呤合成抑制剂AcR发生率MMF也会造成较严重骨髓抑。1（multidrug resistance-1, 基金项目:中国博士后科学基金(20070411151)；重庆市自然科学基金（CSTC，2008BB5229）；重庆市涪陵区自然科学基金（2008-48） Supported by the Chinese Postdoctoral Science Foundation (2