中文摘要：

目的构建具有缺氧调控活性的基因治疗载体,其表达可由缺氧选择性诱导,用于转导基因的可控性表达。方法合成各种缺氧应答基因的缺氧应答元件（HRE）寡核苷酸序列,与巨细胞病毒（CMV）启动子组合,驱动荧光素酶报告基因和治疗基因人红细胞生成素（hEPO）的转录。检测荧光素酶的活性和hEPO的表达以确定其缺氧转录活性。结果在各种缺氧调控载体中,由鼠磷酸甘油酸激酶（mPGK）的HRE与CMV启动子组合而成的缺氧应答启动子显示出高缺氧应答性,而且缺氧诱导的表达水平与完整的CMV启动子在常氧环境下的转录水平相近。结论3HRE/mPGK/CMV缺氧调控载体对于实现治疗基因的精确调控表达可能非常有用。

英文摘要：

Objective To construct hypoxia regulatory vectors which express selectively under hypoxia and to utilize the vectors to express regulatory transduced gene. Methods Hypoxia response element （HRE） oligonucleotides derived from hypoxia response genes were synthesized and linked with CMV promoter to drive luciferase reporter and therapeutic gene transcription. Then the hypoxic transcriptional activation of the constructs was measured by detecting relative luciferase activity and hEPO expression. Results Among five vectors, the combination of 3HRE/mPGK and CMV promoter exhibited excellent hypoxia responsiveness to the similar level to the intact CMV promoter under no rmoxia. Conclusion The 3HRE/mPGK/CMV vector may be especially useful to achieve regulatory therapeutic gene expression precisely.