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第七节 载脂蛋白H
http://www.100md.com 《动脉粥样硬化》

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++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。

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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