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目的研究载脂蛋白AI(apoAI)基因表达调控对血浆高密度脂蛋白(HDL)代谢的影响。方法采用已建立的含小鼠金属硫蛋白I(MT-I)启动子的人apoAI转基因C57BL/6小鼠系,通过Southern及Northern杂交技术检测锌诱导前后人apoAI基因整合和表达的情况。结果转基因小鼠整合4~15拷贝的人apoAI基因。人apoAI基因主要在肝和肾中表达,经重金属锌诱导后,人apoAI基因可在肝、小肠及肾中高效表达。转基因鼠血浆总apoAI水平比对照组明显增高,其中人apoAI水平经锌诱导后增高约46%。与对照组相比,血浆HDL水平在锌诱导前后分别增高约47%和103%。转基因鼠HDL和人apoAI水平间呈显著正相关(r=0.85,P<0.01)。结论ApoAI对血浆HDL水平升高有重要的调节作用,该转基因鼠是进一步研究apoAI在高脂血症时对脂质代谢的影响和抗动脉粥样硬化(AS)作用机制的理想动物模型
Aim To investigate the effect of apoAI gene expression on the metabolism of plasma high density lipoprotein (HDL). Methods The human apoAI transgenic C57BL / 6 mouse line with mouse metallothionein I (MT-I) promoter was used to detect the integration and expression of human apoAI gene before and after zinc induction by Southern and Northern blot. Results Transgenic mice integrated 4-15 copies of human apoAI gene. Human apoAI gene is mainly expressed in liver and kidney. After induced by heavy metal zinc, human apoAI gene can be efficiently expressed in liver, small intestine and kidney. The total plasma apoAI levels in transgenic mice were significantly higher than those in the control group, and the level of human apoAI increased by about 46% after zinc induction. Plasma HDL levels increased by about 47% and 103%, respectively, before and after zinc induction compared with the control group. There was a significant positive correlation between HDL levels and human apoAI levels in transgenic mice (r = 0.85, P <0.01). Conclusion ApoAI plays an important role in the regulation of plasma HDL. The transgenic mouse is an ideal animal model to further study the effect of apoAI on lipid metabolism and anti-atherosclerosis (AS) mechanism in hyperlipidemia