第七节 载脂蛋白H
人载脂蛋白H（human apolipoprotein H,ApoH）又称为β2糖蛋白Ⅰ（β2-glycoprotein,β2-GI），由Schultze等于1961年首先发现，它是人血浆中作为过氯酸可溶性部分存在的一种50kD糖蛋白。
ApoH是由326个氨基酸残基组成的单链多肽，其中含量最丰富的是脯氨酸（共31个），半胱氨酸共有22个，与二硫键的形成有关。含有甘氨酸23个，并与胱氨酸共同形成高频β-转角所必需。ApoH分子量为50kD，具有寡聚多糖的结构，含有5个分支糖胺寡聚多糖侧链，糖链占整个蛋白质分子的19%，系由半乳糖，甘露糖、N-乙酰氨基葡萄糖、岩藻糖及N-乙酰神经氨酸组成。所有寡聚多糖均通过糖基受体序列Asn-X-Ser/Thr而连接到天冬酰胺位点上，分别位于143、164、169、174和234残基位置上。受体序列中间位的“X”为色氨酸（Trp），且这两个Trp在蛋白链中都为同源位点。
因等位基因缺失可引起血清浓度异常，依此提出两个常染色体共显性等位基因-BgN（正常型）和BgD（缺失型）控制ApoH的表达模式：BgNBgN纯合子个体，其ApoH浓度在169～300mg/L；BgNBgD杂合子，血清浓度在60～140mg/L；而BgDBgD纯合子个体则＜50mg/L。BgD缺失型等位基因出现频率在先天愚型人群中＞20%，比健康人群要高。非遗传因素也可以起血清中ApoH含量的变化。因ApoH基因变异，其结构存在多态性，目前认为编码相关的三个普通等位基因即ApoH1、ApoH2和ApoH3、还有ApoH4的存在。三个常染色体的3个等位基因型决定了六种不同形式的表型，共同基因ApoH2出现频率高达90%。
在人血浆中占总量60%的ApoH存在于离心后d＞1.21g/ml底层部分的游离脂蛋白中，余下部分则主要存在于富含TG的脂蛋白中，是CM、VLDL、LDL和HDL的组成成分，又是LPL的激活剂。有报道，ApoH在ApoCⅡ存在时，能提高LPL活性45±17%，而ApoCⅢ则降低ApoH是ApoCⅡ赋予的LPL活性的77%。ApoH还参与凝血机制，因为ApoH与血小板结合，使磷脂带阴电荷，从而减少凝血因子Xa、Va、Ca++与凝血酶原的结合位点或凝血酶原结合到血小板膜上后，通过调节腺苷酸环化酶活性来抑制ADP介导的血小板凝集，它作为一种血浆抑制因子，抑制内源性凝血旁路的接触激活。
在肾小管疾病中，ApoH的检测可作为早期肾小管损伤时的诊断指标，然而灵敏度尚不够高。
健康人血浆中ApoH浓度为193±30mg/L。
(周新 郑芳)
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