关于正常妊娠、分娩及产褥期子宫胎盘循环中激肽释放酶-激肽系统的凝血-纤溶系统研究。

Studies on blood coagulation-fibrinolysis system regarding kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium.

作者信息

Mutoh S, Kobayashi M, Hirata J, Itoh N, Maki M, Komatsu Y, Yoshida A, Sasa H, Kuroda K, Kikuchi Y

机构信息

Division of Perinatal and Maternal Medicine, Akita University School of Medicine, Japan.

出版信息

Agents Actions Suppl. 1992;38 ( Pt 2):320-9.

DOI:

PMID:1462839

Abstract

In our previous study (Adv. Exp. Med & Biol., 247B. 569. 1989, 198B. 41. 1986, blood & vessel, 17: 51. 1986), we reported on the mechanism of coagulation-fibrinolysis system and kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium. The samples were collected from the uterine artery (UA), uterine vein (UV) and peripheral vein (PV). In this study, we tried to elucidate the mechanism of coagulation-fibrinolysis with relation to kks by measuring of Thrombin/Antithrombin III complex (TAT), tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI) complex (tPA.PAI.C), active plasminogen activator inhibitor 1 (active PAI), alpha 2-plasmin inhibitor/plasmin complex (PIC). In 20 normal pregnant women, the levels of TAT, tPA.PAI.C and active PAI significantly increased the first trimester (TAT 4.31 +/- 2.05 ng/ml, tPA.PAI.C 39.52 +/- 17.34 ng/ml, active PAI 39.58 +/- 15.29 ng/ml, n = 20 M +/- SD P < 0.001) to the third trimester (TAT 6.39 +/- 1.93 ng/ml, tPA.PAI.C 57.94 +/- 30.80 ng/ml, active PAI 304.24 +/- 148.64 ng/ml, n = 20 M +/- SD P < 0.001) as compared with those of non-pregnant women (TAT 1.60 +/- 0.89 ng/mg, tPA.PAI.C 11.72 +/- 4.59 ng/ml, active PAI 11.53 +/- 7.48 ng/ml, n = 16 M +/- SD). In utero-placental circulation, the levels of TAT significantly increased (TAT 22.12 +/- 20.03 ng/ml n = 20 M +/- SD P < 0.001) in UV, and tPA.PAI.C and PIC. markedly increased (tPA.PAI.C 93.38 +/- 56.05 ng/ml, PIC 1.03 +/- 0.94 micrograms/ml n = 20 M +/- SD P < 0.02) in UV, but active PAI markedly decreased (active PAI 244.18 +/- 87.55 ng/ml n = 20 M +/- SD P < 0.02) as compared with those in PV (TAT 6.1 +/- 2.09 ng/ml, tPA.PAI.C 59.34 +/- 18.99 ng/ml, PIC 0.49 +/- 0.24 micrograms/ml, active PAI 349.14 +/- 157.34 ng/ml, n = 20 M +/- SD). These findings suggest that the significant increase in those complexes in UA has produced a deposition of fibrin clots in the area in contact with utero-placental blood vessel, although the marked increase in tPA.PAI.C and PIC incompletely inhibited the fibrinolytic activity of tPA by the active PAI. The kks shows a consumption of prekallikrein, LMW-kininogen and HMW-kininogen, and an overproduction of kinin in UV.

摘要

在我们之前的研究中（《实验医学与生物学进展》，247B. 569. 1989；198B. 41. 1986；《血液与血管》，17: 51. 1986），我们报道了正常妊娠、分娩及产褥期子宫 - 胎盘循环中凝血 - 纤溶系统和激肽释放酶 - 激肽系统的机制。样本采集自子宫动脉（UA）、子宫静脉（UV）和外周静脉（PV）。在本研究中，我们试图通过检测凝血酶/抗凝血酶III复合物（TAT）、组织型纤溶酶原激活剂（tPA）、纤溶酶原激活剂抑制剂1（PAI）复合物（tPA.PAI.C）、活性纤溶酶原激活剂抑制剂1（活性PAI）、α2 - 纤溶酶抑制剂/纤溶酶复合物（PIC）来阐明与激肽释放酶 - 激肽系统相关的凝血 - 纤溶机制。在20例正常孕妇中，与非孕妇（TAT 1.60±0.89 ng/mg，tPA.PAI.C 11.72±4.59 ng/ml，活性PAI 11.53±7.48 ng/ml，n = 16，均值±标准差）相比，TAT、tPA.PAI.C和活性PAI水平在孕早期（TAT 4.31±2.05 ng/ml，tPA.PAI.C 39.52±17.34 ng/ml，活性PAI 39.58±15.29 ng/ml，n = 20，均值±标准差，P < 0.001）至孕晚期（TAT 6.39±1.93 ng/ml，tPA.PAI.C 57.94±30.80 ng/ml，活性PAI 304.24±148.64 ng/ml，n = 20，均值±标准差，P < 0.001）显著升高。在子宫 - 胎盘循环中，与外周静脉（TAT 6.1±2.09 ng/ml，tPA.PAI.C 59.34±18.99 ng/ml，PIC 0.49±0.24 μg/ml，活性PAI 349.14±157.34 ng/ml，n = 20，均值±标准差）相比，子宫静脉中TAT水平显著升高（TAT 22.12±20.03 ng/ml，n = 20，均值±标准差，P < 0.001），tPA.PAI.C和PIC显著升高（tPA.PAI.C 93.38±56.05 ng/ml，PIC 1.03±0.94 μg/ml，n = 20，均值±标准差，P < 0.02），但活性PAI显著降低（活性PAI 244.18±87.55 ng/ml，n = 20，均值±标准差，P < 0.02）。这些发现表明，子宫动脉中这些复合物的显著增加在与子宫 - 胎盘血管接触的区域产生了纤维蛋白凝块的沉积，尽管tPA.PAI.C和PIC的显著增加被活性PAI不完全抑制了tPA的纤溶活性。激肽释放酶 - 激肽系统在子宫静脉中显示出前激肽释放酶、低分子量激肽原和高分子量激肽原的消耗以及激肽的过量产生。