雌激素诱导的大鼠肝血窦区域变化。

Estrogen-induced zonal changes in rat liver sinusoids.

作者信息

Raufman J P, Miller D L, Gumucio J J

出版信息

Gastroenterology. 1980 Dec;79(6):1174-7.

Abstract

Estrogen-containing oral contraceptives have been associated with changes in hepatic sinusoids in women. This association has not been studied systematically. To define, quantitate, and locate the estrogen-induced changes within the zones of the hepatic acinus. a morphometric analysis of sinusoids was performed in rat liver. Female rats received oral ethynyl estradiol, dissolved in corn oil, in doses of 0.125 mg/100 g body wt per day for either 2 or 6 wk. Control groups received corn oil in volumes equal to the ethynyl estradiol group or were untreated. After 2 or 6 wk, livers were fixed by perfusion with glutaraldehyde, and 5-microns sections were prepared and analyzed in an automatic image analyzer (Quantimet 720). The ratio of the volume fraction of the sinusoids in zone 1 to that in zone 3 was 2.04 +/- 0.15 (SE) after 2 wk of ethynyl estradiol administration, as compared with 0.87 +/- 0.5 (SE) in rats given corn oil and 0.76 +/- 0.3 (SE) in untreated controls. The differences between the two control groups and the ethynyl estradiol group were significant (P < 0.005). This greater zone 1/zone 3 ratio after ethynyl estradiol was due both to an increased volume fraction of sinusoids in zone 1 as well as to a decreased volume fraction of sinusoids in acinar zone 3, as compared with controls (P < 0.005). The surface to volume ratio of sinusoids, one of the parameters determining the probability of solute-sinusoidal wall interaction, was smaller in zone 1 (P < 0.005) and larger in zone 3 (P < 0.005) in animals treated with ethynyl estradiol than in controls. After 6 wk of ethynyl estradiol administration, the changes in volume fraction persisted. These results indicated that ethynyl estradiol, a synthetic estrogen contained in many oral contraceptives, induced selective zonal changes in rat liver sinusoids. These alterations resulted in the persistent dilatation of sinusoids of acinar zone 1, the acinar inlet, and in the sustained constriction of sinusoids of zone 3, the acinar outlet.

摘要

含雌激素的口服避孕药与女性肝血窦的变化有关。这种关联尚未得到系统研究。为了定义、量化并定位肝腺泡区内雌激素诱导的变化，对大鼠肝脏的血窦进行了形态计量分析。雌性大鼠每天经口给予溶于玉米油中的乙炔雌二醇，剂量为0.125mg/100g体重，持续2周或6周。对照组给予与乙炔雌二醇组体积相等的玉米油，或不进行处理。2周或6周后，通过戊二醛灌注固定肝脏，制备5微米切片，并在自动图像分析仪（Quantimet 720）中进行分析。给予乙炔雌二醇2周后，1区血窦的体积分数与3区血窦体积分数之比为2.04±0.15（标准误），而给予玉米油的大鼠该比值为0.87±0.5（标准误），未处理对照组为0.76±0.3（标准误）。两个对照组与乙炔雌二醇组之间的差异具有统计学意义（P<0.005）。与对照组相比，乙炔雌二醇处理后1区/3区比值升高，这是由于1区血窦体积分数增加以及腺泡3区血窦体积分数降低所致（P<0.005）。在给予乙炔雌二醇的动物中，血窦的表面积与体积之比（决定溶质与血窦壁相互作用概率的参数之一）在1区较小（P<0.005），在3区较大（P<0.005），与对照组相比。给予乙炔雌二醇6周后，体积分数的变化持续存在。这些结果表明，许多口服避孕药中含有的合成雌激素乙炔雌二醇可诱导大鼠肝脏血窦发生选择性区域变化。这些改变导致腺泡入口处1区血窦持续扩张，以及腺泡出口处3区血窦持续收缩。