目的:探讨子痫前期患者外周静脉血清中三磷酸腺苷结合盒转运体A1(ABCA1)蛋白表达的特点,阐明ABCA1对内皮细胞损伤的影响及可能的机制。方法:选取同期住院、年龄、孕周无明显差异的子痫前期患者40例(按病情轻重分为轻度、重度组)及正常妊娠者20名,采用ELISA试剂盒定量检测3组研究对象外周静脉血清中ABCA1及氧化低密度脂蛋白(OX-LDL)表达水平的差异。原代分离并培养上述3组研究对象脐静脉内皮细胞(HUVECs),采用荧光标记的牛血清白蛋白(BSA)检测内皮细胞的单层屏障功能;采用MTT法检测内皮细胞的增殖能力;采用硝酸还原酶法检测内皮细胞的一氧化氮(NO)合成能力;计算OX-LDL/ABCA1比值,并进行相关性分析。结果:与正常妊娠组比较,子痫前期组患者外周静脉血清中ABCA1蛋白表达水平明显降低(P〈0.05),而OX-LDL表达水平及OX-LDL/ABCA1比值明显升高(P〈0.05);ABCA1与OX-LDL表达水平呈明显负相关关系(r=-0.681,P〈0.05)。与正常妊娠组比较,子痫前期组患者通过单层内皮细胞的BSA水平明显升高(P〈0.05),内皮细胞增殖能力明显下降(P〈0.05);内皮细胞分泌NO水平明显降低(P〈0.05)。且病情越严重,上述改变越明显。子痫前期组患者血清中OX-LDL/ABCA1比值与通过内皮细胞的BSA水平呈正相关关系(r=0.791,P〈0.05),与内皮细胞的增殖水平呈负相关关系(r=-0.812,P〈0.05),与内皮细胞中NO水平也呈负相关关系(r=-0.635,P〈0.05)。结论:子痫前期患者血清中ABCA1蛋白表达水平明显下降,引起氧化应激,OX-LDL和ABCA1表达失衡,这与全身血管内皮细胞的损伤密切相关,可能是参与子痫前期发生发展的重要机制之一。
Objective To investigate the expression of ATP binding cassette transporter A1(ABCA1)in serum obtained from peripheral blood of the patients with preeclampsia,and to clarify its effects on the injury of endothelial cells and possible mechanisms.Methods 40 cases of mild or severe preeclampsia women and 20 cases of normal pregnancy women were randomly selected,whose period of hospitalization and gestational age had no significant differences.The expression levels of serum ABCA1 and oxidized low-density lipoprotein(OX-LDL)in peripheral vein blood were determined by using ELISA.The primary isolated and cultured umbilical vein endothelial cells(HUVECs)were obtained from the three groups.The function of endothelial cells was tested on the basis of following aspects:monolayer barrier function was evaluated by transferring fluorescently-labeled BSA across the monolayer HUVECs;the cell proliferation was measured by using MTT assay;the levels of secretory nitric oxide(NO)was assayed by nitrate reductase assay.Results The expression levels of ABCA1 protein in serum of the patients in mild or severe preeclampsia groups were significantly lower,whereas the expression levels of OX-LDL and the ratios of OX-LDL/ABCA1 were significantly higher than those in normal pregnancy group(P〈0.05).There was obviously negative correlation between the levels of ABCA1 and OX-LDL in the patients with preeclampsia(r=-0.681,P〈0.05).Compared with normal pregnancy group,the BSA levels across the monolayer HUVECs of the patients in preeclampsia groups were significantly increased(P〈0.05),the proliferation ability of HUVECs was markedly decreased(P〈0.05),and the level of secretory NO was significantly reduced(P〈0.05).And the more severe the disease,the more significant these changes.The ratio of serum OX-LDL/ ABCA1 was positively correlated with the BSA level(r= 0.791,P〈0.05),and was negatively correlated with the endothelial cell proliferation level(r=-0.812,P〈0.05),and was negatively corr