HEPATIC TRANSPORT OF INDOCYANINE GREEN IN DOGS CHRONICALLY INTOXICATED WITH DIMETHYLNITROSAMINE
HEPATIC TRANSPORT OF INDOCYANINE GREEN IN DOGS CHRONICALLY INTOXICATED WITH DIMETHYLNITROSAMINE
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DOI：
10.1016/0041-008x(84)90213-8
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发表时间：
1984-01-01
影响因子：
3.8
通讯作者：
HANANO, M
中科院分区：
文献类型：
--
作者：
KAWASAKI, S;UMEKITA, N;HANANO, M
在慢性中毒二甲基亚硝胺 (DMN) (2 mg/kg) 的狗中检查吲哚菁绿 (ICG) 的肝脏转运，每周一次，持续 6 周。在病理生理学后果中，谷氨酸丙酮转氨酶（GPT）和血浆总胆汁酸显着升高（P < 0.05），但体重、肝脏湿重、谷氨酸草酰乙酸转氨酶（GOT）、血浆碱性磷酸酶活性、血浆总蛋白和血浆总胆红素无显着差异。通过对中毒狗的肝脏进行组织学检查，观察到门静脉周围、窦周、特别是中央周围区域的纤维化增加，并伴有正常结构的丧失。还证实了门静脉周围和中心周围区域之间的部分纤维桥接，但没有观察到具有再生结节的广泛假分叶。中毒狗的门静脉压增加了.apprx。对照的 50%。在中毒犬中，ICG的血浆消失和胆汁排泄出现延迟，药代动力学参数k12（血浆至肝脏转移速率常数）、V2（肝室分布体积）和CLtot（全身血浆清除率）显着降低，而k23（肝内扩散和转运速率常数）显着增加； V1（血浆室的分布体积）没有改变。肝脏摄取过程中 ICG 内在清除率的降低可能解释了在 DMN 中毒狗中观察到的肝脏 ICG 摄取率的降低。长期中毒 DMN 的狗可能是研究肝功能障碍的良好模型。
Hepatic transport of indocyanine green (ICG) was examined in dogs chronically intoxicated with dimethylnitrosamine (DMN) (2 mg/kg) intraportally once/wk for 6 wk. In pathophysiological consequences, significant increases (P < 0.05) were shown in glutamic-pyruvic transaminase (GPT) and total plasma bile acids, but no significant difference was shown in body weight, liver wet weight, glutamic-oxaloacetic transaminase (GOT), plasma alkaline phosphatase activity, total plasma protein and total plasma bilirubin. By histologic examination of livers from intoxicated dogs, increased fibrosis in periportal, perisinusoidal and especially pericentral areas, with loss of normal architecture, was observed. Partial fibrous bridging between periportal and pericentral areas was also demonstrated, but extensive pseudolobulation with regenerative nodules was not observed. The portal venous pressure of the intoxicated dogs was increased by .apprx. 50% of that of controls. In intoxicated dogs, delays were shown in plasma disappearance and biliary excretion of ICG and significant decreases were observed in the pharmacokinetic parameters k12 (plasma to liver transfer rate constant), V2 (distribution volume of liver compartment) and CLtot (total body-plasma clearance), while a significant increase was observed in k23 (intrahepatic diffusion and transport rate constant); the V1 (distribution volume of plasma compartment) was not altered. The decrease in the intrinsic clearance of ICG for the hepatic uptake process might explain the decrease in ICG uptake rate into the liver which was observed in the DMN-intoxicated dogs. Dogs chronically intoxicated with DMN might be a good model for studying hepatic dysfunction.