妊娠期高血压疾病患者外周血单个核细胞及胎盘晚期糖基化终末产物受体表达及与氧化应激的关系

Alteration of receptor for advanced glycation end products expression in peripheral blood mononuclear cells and placentas in pregnancy induced hypertension and its relationship with oxidative stress

目的探讨外周血单个核细胞(PBMCs)及胎盘晚期糖基化终末产物受体(RAGE)表达及其与氧化应激的关系,了解其在妊娠期高血压疾病发生、发展中的作用。方法同期收治的轻、中度妊娠期高血压疾病患者15例,重度妊娠期高血压疾病患者15例,正常晚期妊娠20例,抽取肘静脉血及留取胎盘,用蛋白质免疫印迹法(Westernblot)测定PBMCs及胎盘RAGE蛋白的表达,并测定血浆及胎盘丙二醛(MDA)水平及超氧化物歧化酶(SOD)活性。结果妊高征患者血浆及胎盘MDA水平高于正常晚期妊娠组,且重度妊娠期高血压疾病患者较轻、中度妊娠期高血压疾病患者升高(P均<0.01);轻、中度妊娠期高血压疾病组血浆及胎盘SOD活性低于正常晚期妊娠组(血浆P<0.01,胎盘P<0.05),在重度妊娠期高血压疾病组血浆及胎盘SOD活性进一步降低,低于轻、中度妊娠期高血压疾病组(血浆P<0.05,胎盘P<0.01);RAGE蛋白在正常晚期妊娠组、轻、中度妊娠期高血压疾病组和重度妊娠期高血压疾病组胎盘中的表达量分别为0.305±0.045、0.439±0.047、0.975±0.057,在PBMCs中的表达量分别为0.301±0.067、0.399±0.062、0.572±0.089,RAGE蛋白在轻、中度妊娠期高血压疾病组胎盘和PBMCs中的表达高于正常晚期妊娠组(P均<0.01),在重度妊娠期高血压疾病组中的表达高于正常晚期妊娠组及轻、中度妊娠期高血压疾病组(P均<0.01);PBMCs内RAGE蛋白表达与血浆MDA水平呈中度正相关(轻、中度妊娠期高血压疾病组:r=0.46,P<0.05;重度妊娠期高血压疾病组:r=0.47,P<0.05);胎盘RAGE蛋白表达与胎盘MDA水平呈高度正相关(轻、中度妊娠期高血压疾病组:r=0.82,P<0.01;重度妊娠期高血压疾病组:r=0.88,P<0.01)。结论 PBMCs及胎盘RAGE表达与氧化应激相互关联,共同在妊高征的发病机制中发挥了重要作用。

Objective To investigate the alteration of receptor for advanced glycation end products （RAGE） expression in peripheral blood mononuclear cells （PBMCs） and placentas in women with pregnancy induced hypertension（PIH） and to determine its relationship with oxidative stress. Methods RAGE expression in PBMCs and placentas was determined with western blot, and malonyl diaidehyde（MDA） and superoxide dismutase（SOD） in plasma and Placentas were measured spectrophotometrically in 15 women with mild/moderate PIH, 15 women with severe PIH and 20 healthy pregnant women. Results MDA levels were increased in plasma and placentas of women with PIH compared with healthy pregnant women（ P 〈0.01）, and the levels were higher in severe PIH than in mild/moderate PIH（ P 〈0.01）. SOD activities in plasma and placentas were reduced in mild/moderate PIH than in healthy pregnancy （ P 〈0.01 in plasma and P 〈0.05 in placentas） ,and were further decreased in severe PIH than in mild/moderate PIH （ P 〈0.05 in plasma and P 〈0.01 in placentas）. RAGE expression in placentas of healthy pregnancy, mild/moderate PIH and severe PIH was 0. 305 ± 0. 045,0. 439 ± 0. 047 and 0. 975 ± 0. 057 respectively. Its expression in PBMCs of healthy pregnancy, mild/moderate PIH and severe PIH was 0. 301± 0. 067, 0. 399 ± 0. 062 and 0. 572 ± 0. 089 respectively. RAGE expression in PBMCs and placentas was higher in mild/moderate PIH than in healthy pregnancy （ P 〈0.01） ,and was further increased in severe PIH than in mild/moderate PIH and healthy pregnancy （ P 〈0.01）. RAGE expression in placentas was positively correlated with MDA levels in placentas （ r =0.82, P 〈0.01 in mild/ moderate PIH and r =0.88, P 〈0.01 in severe PIH）,and there was a moderately positive correlation between plasma MDA and RAGE expression in PBMCs （ r =0.46, P 〈0.05 in mild/moderate PIH and r =0.47, P 〈0.05 in severe PIH）. Conclusion RAGE expression in PBMCs and placentas is enhanced in PIH and correlated with oxidative stress, and plays an important role in the pathogenesis of PIH.