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Improvement of Portal Hypertension and Hepatic Blood Flow in Liver Cirrhosis by Estrogen

雌激素对肝硬化门脉高压和肝血流量的改善作用

基本信息

批准号：
16590649
负责人：
SAKAMOTO Masaharu
金额：
$ 1.6万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590649/
关键词：
estrogen nitric oxide portal hypertension エンドセリン-1 肝類洞内皮細胞 estrogen 肝血流門脈圧

项目摘要

Background : In this study, we investigated the effects of estrogen on nitric oxide synthase activity and nitric oxide production using the cirrhotic rat liver.Material and Methods : Cirrhosis was induced by dimethylnitrosamine. Estradiol valerate was subcutaneously injected 2 times at week 4 after dimethylnitrosamine treatment. Furthermore, subcutaneous injection of an estrogen receptor antagonist, ICI-182.780, was performed 2 days before administration of estradiol valerate. Portal pressure and hepatic blood flow were measured. Nitric oxide synthase activity was assessed by L-citrulline generation. Sinusoidal endothelial cells were isolated from the cirrhotic rat liver and cultured. The cells were incubated with estradiol and/or ICI-182.780 for 24 hours. Images for nitric oxide in sinusoidal endothelial cells were obtained using diaminofluorescein-2 diacetate.Results : Cirrhotic rats treated with estradiol valerate showed a significant decrease in portal pressure and a significant increase in hepatic blood flow compared to those of control cirrhosis rats. However, in cirrhotic rats treated with ICI-182.780, the reduction of portal pressure and elevation of hepatic blood flow were completely inhibited. In cirrhotic rats treated with estradiol valerate, nitric oxide synthase activity was increased compared to that in control cirrhotic rats. The fluorescent level of intracellular nitric oxide in estradiol-stimulated cultured sinusoidal endothelial cells was higher than that in non-treated sinusoidal endothelial cells.Conclusions : The present study indicated that estrogen plays an important role in the enhancement of nitric oxide production in sinusoidal endothelial cells of cirrhotic liver and reduces the portal pressure in cirrhotic rats.

背景：在本研究中，我们观察了雌激素对肝硬变大鼠肝脏一氧化氮合酶活性和一氧化氮产生的影响。材料和方法：二甲基亚硝胺诱导大鼠肝硬变。二甲基亚硝胺治疗后第4周皮下注射戊酸雌二醇2次。此外，皮下注射雌激素受体拮抗剂ICI-182.780是在注射戊酸雌二醇前2天进行的。测量门静脉压力和肝血流量。用L-瓜氨酸生成法测定一氧化氮合酶活性。从肝硬变大鼠肝脏分离培养肝窦内皮细胞。细胞与雌二醇和/或ICI-182.780孵育24小时。结果：与对照组相比，戊酸雌二醇组大鼠的门脉压力显著降低，肝血流量显著增加。而在经ICI-182.780治疗的肝硬变大鼠中，门脉压力的降低和肝血流量的升高被完全抑制。在接受戊酸雌二醇组的肝硬变大鼠中，一氧化氮合酶活性较对照组升高。结论：雌激素在肝硬变大鼠肝窦内皮细胞产生一氧化氮的过程中起重要作用。