载脂蛋白(a)促进表达人apo(a)基因的WHHL转基因家兔产生复合动脉粥样硬化

Complicated atherosclerosis effect of apo (a) promotes in WHHL rabbits capable to express human apo (a) gene

目的:研究载脂蛋白(a)[apo(a)]对表达人apo(a)基因的WHHL转基因家免动脉粥样硬化的影响。方法:制备表达人apo(a)的WHHL转基因家兔,比较WHHL转基因家兔与WHHL非转基因家兔的动脉粥样硬化病变程度及病变特点。结果:WHHL转基因家兔血浆中apo(a)浓度大约为150 mg·L-1,血浆脂质水平与WHHL非转基因兔相近。WHHL转基因家兔的病变以纤维斑块和粥样变即复合病变为主,而非转基因家兔的病变则大多为脂肪条纹。兔疫组化研究结果表明转基因WHHL家兔的病变中的纤维帽主要由平滑肌细胞构成,病变的坏死灶内含有大量的有巨噬细胞衍变而来的泡沫细胞。apo(a)主要沉积在平滑肌比较丰富的区域,另一个比较明显的特征是转基因家兔的病变内有大量钙化形成,而在非转基因家兔体内则几乎没有。结论:apo(a)促进表达人apo(a)基因的WHHL转基因家兔产生复合动脉粥样硬化。

Objective：To evaluate if increase of plasma apo（a） levels may worse atherosclerosis in the Watanabe hereditary hyperlipidemic （WHHL） rabbits expressing human apo（a） gene. Methods： The mode of the WHHL rabbits with capacity to express human apo（a） gene was developed. The severity and features of atherosclerotic lesions of transgenic （Trg） WHHL rabbits were compared to those of nontransgenic WHHL rabbits. Results： The plasma apo（a） concentration of Trg WHHL rabbits reached for 150 mg·L^-1 The plasma lipid level of Trg WHHL rabbits was no significantly different from the one of non-Trg WHHL rabbits. The Trg WHHL rabbits mainly suffered from complicated arthrosclerosis, featuring fibrous plaques and atheroma. The non-Trg WHHL rabbits had lesions predominated in fatty streak. An immunohistochemical study revealed that the cap of the lesions in the Trg WHHL rabbits were composed of smooth muscle cells and the core of the lesions contained a lot of macrophage-derived foam cells. Deposition of apo（a） was mainly present in the area enriched in smooth muscle cells. In particular, the lesions of Trg WHHL rabbits were often associated with marked calcification, which was barely evident in nonTrg rabbits. Conclusions： Apo（a） accelerates the fibrous plaque formation and calcification in WHHL rabbits.