Rincón A R, Covarrubias A, Pedraza-Chaverrí J, Poo J L, Armendáriz-Borunda J, Panduro A
Institute of Molecular Biology in Medicine and Hospital Civil de Belén, CUCS, University of Guadalajara, Jalisco, México.
Exp Toxicol Pathol. 1999 May;51(3):199-205. doi: 10.1016/S0940-2993(99)80094-3.
The pathogenesis of renal function alteration associated with liver disease remains to be elucidated. Although different experimental animal models have been utilized in order to explain such pathophysiological state, none of them have completely explained the mechanisms involved. In this study we performed differential hemodynamic, hepatic and renal function alteration studies after induction of acute liver damage via intragastric administration of a single dose of CCl4 to cirrhotic and non-cirrhotic rats. Cirrhotic rats with acute liver damage exhibited a significant decrease in mean arterial pressure followed by a decreased glomerular filtration rate, urinary sodium concentration and an induction of plasma renin concentration and activity. At the same time, a significant association between oliguria and mortality was observed. The renal histopathological studies revealed glomeruli with mesangial hypercellularity and thickening of capillary wall, but not tubular epithelial injury. All these alterations were not detected in the control group, i.e. by non-cirrhotic rats with acute liver damage. This study suggests that the effect of CCl4 on kidney structure and function depends on the functional state of the liver. Since this experimental model of acute liver damage in cirrhotic rats presents hemodynamics and renal function alterations similar to those observed in the hepatorenal syndrome in man, it could be utilized to study the pathogenesis of renal function alterations associated with liver damage.
与肝脏疾病相关的肾功能改变的发病机制仍有待阐明。尽管已使用不同的实验动物模型来解释这种病理生理状态,但它们均未完全解释其中涉及的机制。在本研究中,我们通过向肝硬化和非肝硬化大鼠胃内单次注射四氯化碳诱导急性肝损伤后,进行了血流动力学、肝脏和肾功能改变的差异研究。急性肝损伤的肝硬化大鼠平均动脉压显著降低,随后肾小球滤过率、尿钠浓度降低,血浆肾素浓度和活性升高。同时,观察到少尿与死亡率之间存在显著关联。肾脏组织病理学研究显示肾小球系膜细胞增多和毛细血管壁增厚,但未见肾小管上皮损伤。对照组即急性肝损伤的非肝硬化大鼠未检测到所有这些改变。本研究表明,四氯化碳对肾脏结构和功能的影响取决于肝脏的功能状态。由于肝硬化大鼠急性肝损伤的该实验模型呈现出与人类肝肾综合征中观察到的血流动力学和肾功能改变相似的情况,因此可用于研究与肝损伤相关的肾功能改变的发病机制。