性激素对N-甲基四唑硫醇诱导的大鼠低凝血酶原血症的影响。

Effect of sex hormones on hypoprothrombinemia induced by N-methyltetrazolethiol in rats.

作者信息

Uchida K, Shike T, Kakushi H, Takase H, Nomura Y, Harauchi T, Yoshizaki T

出版信息

Thromb Res. 1985 Sep 15;39(6):741-50. doi: 10.1016/0049-3848(85)90258-0.

Abstract

N-Methyltetrazolethiol (NMTT) increased prothrombin time (PT) and decreased plasma factor VII and prothrombin levels only in vitamin K-deficient male rats. In female rats identical treatment with NMTT did not produce hypoprothrombinemia. Conventional and germ-free rats displayed no significant difference in the manifestation of hypoprothrombinemia, but the increase of PT in NMTT-treated vitamin K-deficient rats was greater in the germ-free males. Estradiol administration or castration of male rats retarded manifestation of vitamin K deficient syndromes such as increases of PT and activated partial thromboplastin time (APTT), decreases of plasma factor VII and prothrombin levels, and increases of plasma and liver descarboxyprothrombin (PIVKA) levels, and testosterone injection to the castrated rats restored these changes. In female rats testosterone treatment or castration enhanced the manifestation of hypoprothrombinemia and estradiol treatment to the castrated females retarded it. Gamma-glutamyl-carboxylase activity was increased by vitamin K-deficiency but not inhibited by testosterone or NMTT. These data suggest that estrogen protects the rat against manifestation of hypoprothrombinemia even with NMTT treatment, while androgen enhances vitamin K deficiency, and supplementation of vitamin K prevents its deficiency in NMTT-treated rats.

摘要

N-甲基四唑硫醇（NMTT）仅在维生素K缺乏的雄性大鼠中延长了凝血酶原时间（PT），并降低了血浆因子VII和凝血酶原水平。在雌性大鼠中，相同的NMTT处理并未导致低凝血酶原血症。普通大鼠和无菌大鼠在低凝血酶原血症的表现上没有显著差异，但在经NMTT处理的维生素K缺乏的无菌雄性大鼠中，PT的升高幅度更大。给雄性大鼠注射雌二醇或进行去势会延缓维生素K缺乏综合征的表现，如PT和活化部分凝血活酶时间（APTT）的增加、血浆因子VII和凝血酶原水平的降低以及血浆和肝脏脱羧凝血酶原（PIVKA）水平的增加，而给去势大鼠注射睾酮可恢复这些变化。在雌性大鼠中，睾酮处理或去势会增强低凝血酶原血症的表现，而给去势雌性大鼠注射雌二醇则会延缓这种表现。维生素K缺乏会增加γ-谷氨酰羧化酶的活性，但睾酮或NMTT不会抑制该活性。这些数据表明，即使在NMTT处理的情况下，雌激素也能保护大鼠免受低凝血酶原血症的影响，而雄激素会加重维生素K缺乏，补充维生素K可预防NMTT处理大鼠的维生素K缺乏。