摘要目的 通过研究妊娠期高血压患者(HDP)疾病发生前血浆脂代谢相关蛋白的改变,初步探讨血浆载脂蛋白C4(APOC4)升高在HDP发生中的作用机制.方法 采用巢式病例对照研究,收集2014年11月至2017年3月在广州市妇女儿童医疗中心常规产检,并分娩或剖宫产孕妇血浆.采用非标记质谱法筛选12对HDP患者与正常妊娠者20周前血浆脂代谢相关蛋白的表达差异,并采用48对HDP患者与正常妊娠者20周前血浆样本进行验证;研究两组差异倍数最显著的脂代谢相关蛋白APOC4对人脐静脉内皮细胞(HUVEC)单层通透性和一氧化氮分泌的影响.组间比较使用One-way ANOVA,以P<0.05为差异有统计学意义.结果 与正常对照相比,HDP患者妊娠20周前血浆脂代谢相关蛋白APOC4、脂肪酸结合蛋白4(FABP4)、载脂蛋白E(APOE)、载脂蛋白C3(APOC3)和 β2糖蛋白1(APOH)分别上调至1.94倍、1.82倍、1.59倍、1.55倍和1.38倍,磷脂转运蛋白(PLTP)下调至0.78倍,差异有统计学意义(t值分别为2.499,2.497,2.081,2.098,2.426和2.564,P均<0.05).细胞实验显示50 ng/ml APOC4可增加20％HUVEC细胞的通透性(F=455.4,P<0.01),使血管舒张因子一氧化氮水平下调25％(F=61.92,P<0.01).结论 HDP发生前,患者血浆脂质代谢蛋白水平已发生改变,存在脂代谢异常.其中,APOC4可能通过增加血管内皮细胞通透性,抑制内皮源性NO分泌,造成内皮细胞损伤和功能障碍.

abstractsObjective Find abnormal changes of plasma lipid metabolism-related proteins before 20 weeks of gestation in patients with hypertensive disorder of pregnancy(HDP), and preliminarily investigate the role of plasma apolipoprotein C4 elevation in HDP. Methods A nested case-control study was used. The plasma were collected from pregnant women who underwent routine prenatal examination in Guangzhou Women and Children's Medical Center from November 2014 to March 2017. Label-free mass spectrometry was used to detect the differences in plasma lipid metabolism-related proteins before 20 weeks of gestation between 12 pairs of HDP patients and normal controls, and different 48 pairs of samples were used for verification. The protein with the most significant difference multiples was screened to study its effects on monolayer permeability and nitric oxide secretion of endothelial cells. One-way ANOVA was used for comparison between groups, and P<0.05 was considered as statistically significant difference. Results Compared with the control, the lipid metabolism-related proteins, APOC4, Fatty acid-binding protein 4 (FABP4), Apolipoprotein E (APOE), Apolipoprotein C3 (APOC3) and Beta-2-glycoprotein 1(APOH) raised to 1.94, 1.82, 1.59, 1.55 and 1.38 times, phospholipid transfer protein (PLTP) decreased to 0.78 times in&nbsp;plasma before 20 weeks of pregnancy of patients with HDP (t value were 2.499, 2.497, 2.081, 2.098, 2.426 and 2.564, respectively, P<0.05). Cell experiments results showed that 50 ng / ml APOC4 significantly increased 20％ HUVEC single layer cell permeability to FITC-labeled dextran (F=455.4, P<0.01), and significantly decreased the level of nitric oxide in the supernatant of HUVEC culture by 25％ (F=61.92, P<0.01). Conclusions Before diagnosis, plasma protein levels involved in lipid metabolism in HDP patients have been changed, resulting in abnormal lipid metabolism. APOC4 can increase the permeability of vascular endothelial cells, inhibit endothelial source of NO secretion, cause endothelial dysfunction.