摘要
背景与目的:
妊娠高血压疾病(简称妊高征),是引起孕产妇和围产儿死亡的主要原因,但其确切病因和发病机制至今尚不明了。近年来发现,在妊高征患者血清中存在有抗血管紧张素ⅡAT_1受体的自身抗体(AT_1-AA),这种自身抗体具有类激动剂样的增加细胞内Ca~(2+)浓度的作用,还可以介导胎盘组织氧化应激和炎症反应。然而,血管紧张素Ⅱ(AngⅡ)的主要生理作用部位是血管,AT_1-AA对血管功能有何影响尚未有人进行过研究。
方法:
采集妊高征患者血清标本30例,同质正常孕妇血标本30例;合成人AT_1受体胞外第二环功能表位肽段(165-191位);用SA-ELISA方法检测血清AY_1-AA;用MAb Trap Kit试剂盒对抗血清中的抗体IgG进行提取和纯化;用血管环/微血管环技术观察AT_1-AA对大鼠离体主动脉、冠状动脉环和大脑中动脉的影响。
结果:
1.妊高征患者血清中AT_1-AA的阳性率及浓度明显升高:与同质的正常孕妇(合格标本21份)相比,妊高征患者(合格标本26份)血清中AT_1-AA的阳性率(8.3%vs.57.5%,P＜0.01)和浓度明显增高。
2.AT_1-AA可以增强大鼠主动脉血管环的收缩张力:10~(-6)mol/L的AT_1-AA可使大鼠主动脉血管环的最大收缩张力从对照组的1.02±0.04(g)增加到1.72±0.17(g)(P＜0.01),阴性抗体组则无影响:此作用与Ang-Ⅱ对大鼠主动脉血管环的收缩张力相同:100nmol/L的losartan(ATI-受体的阻断剂)可以有效地拮抗AT_1-AA和Ang-Ⅱ对于血管坏收缩张力的影响。
3.AT_1-AA可以增强大鼠冠脉和大脑中动脉微血管环的收缩张力:10~(-7)mol/L的AT_1-AA可使大鼠冠脉和大脑中动脉血管环的最大收缩张力比阴性抗体组升高,用100 nmol/L的losartan可以有效地拮抗这种效应。
结论:
1.妊高症患者血清中AT_1-AA阳性率及浓度均高于正常孕妇对照组;
2.AT_1-AA与血管紧张素Ⅱ一样,能剂量依赖性地增加主动脉血管环收缩张力,其效应可被AT_1受体阻断剂Losartan所阻断,提示该效应是通过对血管壁上AT_1受体的激动剂样刺激效应实现的。
3.AT_1-AA还可以提高离体大鼠冠脉和大脑中动脉的最大收缩张力,产生AT_1受体激动剂样效应。
Background and Aim:
Preeclampsia is the leading cause of maternal and fetal death,but its etiopathogenisis and pathogenesis are still unclear.In recent years,autoantibodies against angiotensinⅡAT_1 receptors (AT_1-AA)have been found in the sera of patients with preeclampsia.It can play an agonistic role in increasing intracellular Ca~(2+)concentration,and induce oxidative stress and inflammatory reaction in placenta.It is well known that the main target of angiotensinⅡis vessel,however,the direct effect of AT_1-AA on blood vessel is unknown,and need to be determined.
Methods:
Collecting 30 blood samples from preeclamptic women and 30 cases from homogeneity normal pregnant women as control;synthesizing the antigenic peptide corresponding to the second extracellular loop of human angiotensinⅡAT_1 receptors(165-191).Detecting the titers of AT_1-AA from two groups by SA-ELISA;MAb Trap Kit for IgG extraction and purification; Using isolated rat aorta/microvascular ring to observe the effects of AT_1-AA on thoracic aorta, coronary artery and middle cerebral artery activities.
Results:
1.The titre and positive rate of AT_1-AA from preeclamptic patients remarkably increase:
Compared with homogeneity normal pregnant women(21 qualified),the positive rate(8.3% vs.57.5%,p＜0.01)and titers of AT_1-AA from preeclamptic patients(26 qualified)were significant increased.
2.AT_1-AA can increase the aortic vascular contractile tension:
At the dose of 10~(-6)mol/L,AT_1-AA increased the peak systolic tension from the control of 1.02±0.04(g)to 1.72±0.17(g)(p＜0.01),no change was observed in control;Ang-Ⅱshowed similar increasing effects;and both of the increasing effects caused by AT_1-AA and Ang-Ⅱcould be blocked by 100 nmol/L Losartan(the blocker of AT_1-R).
3.AT_1-AA can increase the coronary artery and middle cerebral artery contractile tension:
At the dose of 10~(-7)mol/L,AT_1-AA increased the peak systolic tension of coronary artery and middle cerebral artery,which was higher than control.Effects could be blocked by 100nmol/L Losartan.
Conclusion:
1.Compared with control,titers and positive rate of AT_1-AA from preeclamptic patients were both increased.
2.Just like angiotensinⅡ,the AT_1-AA could dose-dependently increase the contractile tension of the aortic vascular ring,and the effects could be blocked by Losartan.These indicated that the effects of antibodies were induced by their stimulatory agonist-like activities on AT_1-receptors.
3.The AT_1-AA could increase max contractile tension of coronary artery and middle cerebral artery,and would bring about receptor agonist-like activities.
引文
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