Yokoyama Yukihiro, Toth Balazs, Kitchens William C, Schwacha Martin G, Rue Loring W, Bland Kirby I, Chaudry Irshad H
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Surg Res. 2004 Sep;121(1):25-30. doi: 10.1016/j.jss.2004.03.012.
The fine balance between vasoconstrictors and vasodilators maintains portal circulation. Studies have shown that portal response to endothelin-1 (ET-1), a potent vasoconstrictor, is enhanced following hemorrhagic-shock, which subsequently leads to the impaired hepatic circulation and hepatic damage. Although protective effects of 17beta-estradiol (E(2)) against hepatic damage following trauma-hemorrhage have been observed, it remains unknown whether E(2) directly improves hepatic circulation. We hypothesized that the salutary effects of E(2) are mediated, at least in part, by the attenuation of portal response to ET-1 following trauma-hemorrhage.
Male adult Sprague-Dawley rats were randomly assigned to sham operation or trauma-hemorrhage with or without in vivo E(2) treatment. Trauma-hemorrhage included midline laparotomy and approximately 90 min of hemorrhagic shock (35 mmHg), then resuscitation with four times the shed blood volume with Ringer's lactate solution over 60 min. For the E(2) treatment group, 1 mg/kg of E(2) was added to the Ringer's lactate solution. At 5 h after the end of resuscitation, the liver was isolated and perfused in vitro to measure portal pressure responses to exogenous ET-1 (60 pmol in 150 ml perfusate, bolus) with or without E(2) (1,500 pg/ml).
Peak portal pressure after the administration of ET-1 was significantly higher in vehicle-treated trauma-hemorrhage group compared with the sham group. This effect was significantly attenuated in the E(2) treatment group. Furthermore, E(2) treatment restored bile production and prevented hepatic damage following trauma-hemorrhage.
The beneficial effects of estradiol observed following trauma-hemorrhage, at least partly, are caused by the attenuation of portal pressure response to increased ET-1.
血管收缩剂和血管舒张剂之间的精细平衡维持着门静脉循环。研究表明，出血性休克后，门静脉对内皮素 -1（ET -1，一种强效血管收缩剂）的反应增强，随后导致肝循环受损和肝损伤。尽管已观察到17β -雌二醇（E₂）对创伤性出血后肝损伤具有保护作用，但E₂是否直接改善肝循环仍不清楚。我们推测，E₂的有益作用至少部分是通过减轻创伤性出血后门静脉对ET -1的反应来介导的。
成年雄性Sprague - Dawley大鼠被随机分为假手术组或创伤性出血组，创伤性出血组又分为接受或未接受体内E₂治疗的亚组。创伤性出血包括中线剖腹术和大约90分钟的出血性休克（35 mmHg），然后在60分钟内用四倍失血量的乳酸林格氏液进行复苏。对于E₂治疗组，在乳酸林格氏液中加入1 mg/kg的E₂。复苏结束后5小时，分离肝脏并进行体外灌注，以测量门静脉对外源性ET -1（150 ml灌注液中60 pmol，推注）的压力反应，灌注液中加入或不加入E₂（1500 pg/ml）。
与假手术组相比，给予ET -1后，未接受E₂治疗的创伤性出血组门静脉压力峰值显著更高。在E₂治疗组中，这种效应显著减弱。此外，E₂治疗恢复了胆汁生成并预防了创伤性出血后的肝损伤。
创伤性出血后观察到的雌二醇的有益作用至少部分是由门静脉对ET -1增加的压力反应减弱所致。
