氧化修饰和乙酰修饰低密度脂蛋白在A型清道夫受体基因敲除小鼠的清除

The clearance of oxidized-LDL and acetylated-LDL in AI/II scavenger receptor knockout mice

目的：阐明清道夫ＡＩ／Ｉ受体（ＳＲ－ＡＩ／Ｉ）在体内ＯＸ－ＬＤＬ和ＡＣ－ＬＤＬ清除中的作用和重要性。方法：观察同位素标记化学修饰ＬＤＬ在ＳＲ－ＡＩ／Ｉ基因敲除和正常小鼠血浆的清除率和同位素标记的ＬＤＬ在体内主要器官的分布。结果：ＯＸ－ＬＤＬ在正常小鼠血浆清除是非常快的，在５ｍｉｎ内，注入量的９０％即被清除。在ＳＲ－ＡＩ／Ｉ基因敲除小鼠，ＯＸ－ＬＤＬ在血浆的清除速率和正常小鼠相同。ＡＣ－ＬＤＬ的清除在对照组和ＳＲ－ＡＩ／Ｉ受体敲除小鼠也相似。同位素标记的ＡＣ－ＬＤＬ在血浆的清除能够完全被５０倍高剂量未标记的ＡＣ－ＬＤＬ阻断，但同样剂量的未标记的ＡＣ－ＬＤＬ仅能抑制ＯＸ－ＬＤＬ在血浆清除的５％。ＯＸ－ＬＤＬ和ＡＣ－ＬＤＬ主要被肝脏清除。组织器官放射性标记的ＯＸ－ＬＤＬ和ＡＣ－ＬＤＬ的分布在正常小鼠和ＳＲ－ＡＩ／Ｉ基因敲除小鼠没有差异。结论：ＳＲ－ＡＩ／Ｉ受体在体内ＯＸ－ＬＤＬ清除过程中不起主要作用。

AIM: To determine the importance of SR-AI/II in the removal of modified low density lipoprotein (LDL) from the bloodstream in vivo. METHOD:To observe the clearance rate of modified LDL in the plasma of SR-AI/II knockout and control mice. RESULTS: Clearance rate from plasma of oxidized LDL in normal mice was very rapid, and over 90% of injected dose was removed from the blood within 5 minutes. Clearance rates of oxidized LDL were equally high in SR-AI/II gene knockout mice. Similarly, there was no difference in the clearance rate of acetyl LDL in wild-type and SR-AI/II gene knockout animals. The plasma clearance or radio-iodinated acetyl LDL was almost fully blocked by a 50-folds excess of unlabelled acetyl LDL, but the latter only inhibited oxidized LDL clearance by about 5%. Both AC-LDL and OX-LDL were mostly cleared from plasma by the liver. There was no difference in the tissue distribution of modified LDL in control and knockout mice. CONCLUSION: SR-AI/II does not play a significant role in the removal of oxidized LDL from plasma.