Yasuda K, Takashima M, Sawaragi I
Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
Biol Reprod. 1995 Aug;53(2):244-52. doi: 10.1095/biolreprod53.2.244.
We evaluated the effects of estrogen, progestin, and cigarette smoke extract (CSE) on plasma platelet-activating factor (PAF) acetylhydrolase (AH; PAF-AH) activity in rats. The effects on rat tissues of an i.v. injection of PAF were studied as part of our investigation of the mechanisms involved in thrombotic episodes. Plasma PAF-AH activity in adult female rats (14 wk of age) treated with 17 alpha-ethynylestradiol (100 micrograms/kg, 5 days) was decreased by 70%. Medroxyprogesterone (50 mg/kg, 5 days) increased PAF-AH activity by 50%. CSE (0.5 cigarette/kg, 5 days) did not alter PAF-AH activity during the treatment. However, a combination of CSE and 17 alpha-ethynylestradiol decreased plasma PAF-AH activity by 90%. The decrease in PAF-AH activity was age-dependent. The effect of medroxyprogesterone on plasma PAF-AH activity was not influenced by CSE. When PAF (5-40 nmol/kg) was injected i.v. into untreated adult female rats, 9 of 16 animals died after a 20-nmol/kg dose of PAF. Macroscopic findings included hemorrhage, hyperemia, and congestion in the lungs and heart, and necrosis-like changes in the gastrointestinal tract. Microscopically, thrombi were observed in the lungs and heart. When PAF was administered to adult female rats pretreated with sex steroid hormones, the mortality of rats with low plasma PAF-AH activity caused by 17 alpha-ethynylestradiol was increased but that of rats with high PAF-AH activity caused by medroxyprogesterone was decreased. Thus, PAF and PAF-AH may play important roles in the thrombotic episodes known to occur in female smokers who use oral contraceptives.
我们评估了雌激素、孕激素和香烟烟雾提取物（CSE）对大鼠血浆血小板活化因子（PAF）乙酰水解酶（AH；PAF-AH）活性的影响。作为我们对血栓形成发作所涉及机制研究的一部分，研究了静脉注射PAF对大鼠组织的影响。用17α-乙炔雌二醇（100微克/千克，5天）处理的成年雌性大鼠（14周龄）血浆PAF-AH活性降低了70%。甲羟孕酮（50毫克/千克，5天）使PAF-AH活性增加了50%。CSE（0.5支香烟/千克，5天）在治疗期间未改变PAF-AH活性。然而，CSE与17α-乙炔雌二醇联合使用使血浆PAF-AH活性降低了90%。PAF-AH活性的降低与年龄有关。甲羟孕酮对血浆PAF-AH活性的影响不受CSE的影响。当将PAF（5-40纳摩尔/千克）静脉注射到未处理的成年雌性大鼠体内时，16只动物中有9只在注射20纳摩尔/千克剂量的PAF后死亡。宏观表现包括肺和心脏出血、充血，以及胃肠道的坏死样改变。显微镜下，在肺和心脏中观察到血栓。当将PAF给予经性类固醇激素预处理的成年雌性大鼠时，由17α-乙炔雌二醇导致血浆PAF-AH活性低的大鼠死亡率增加，但由甲羟孕酮导致PAF-AH活性高的大鼠死亡率降低。因此，PAF和PAF-AH可能在已知发生于使用口服避孕药的女性吸烟者的血栓形成发作中起重要作用。
