转基因小鼠人载脂蛋白AI基因表达对血浆高密度脂蛋白的影响

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

The effect of expressed human apolipoprotein AI on plasma high density lipoprotein level in transgenic mice

OBJECTIVE: To study the regulation of human apolipoprotein AI(h-apo AI) gene expression and its role in high density lipoprotein (HDL) metabolism. METHODS: Transgenic C57BL/6 mice established in this laboratory with human apoAI gene containing mouse metallothionein-I(MT-I) promoter were used for investigation. RESULTS: Southern blot identified the presence of 4-15 copies of h-apo AI gene in the transgenic mice. Northern blot showed that human apo AI mRNA was expressed mainly in the liver and kidneys, and the high level of h-apo AI mRNA was obtained in liver, kidneys and small intestine after Zinc(Zn) induction. Total Plasma apoAI Level in transgenic mice was significantly increased than that in the controls, and a high h-apoAI level was detected in the transgenic mice (46% increased after Zn induction). Additionally, total and HDL cholesterol levels were noticed to be highly increased to 47% before and 103% after Zn induction in the transgenic mice comparing to that of the controls. The plasma HDL and h-apoAI levels were significantly correlated (r = 0.85, P < 0.01) in the transgenic mice. CONCLUSION: Apo AI has a profound effect on regulating HDL levels in the transgenic mice. This animal model is considered appropriate for studying the effect of apoAI on lipid metabolism and the mechanism combating atherogenesis.