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Renin-angiotensin system in the pathogenesis of liver fibrosis

World Journal of Gastroenterology 2009年第21期15卷 2579-2586页

作者： Regina Maria Pereira Robson Augusto Souza dos Santos filipi leles da costa dias Mauro Martins Teixeira Ana Cristina Simoes e Silva Department of Pediatrics Faculty of MedicineFederal University of Minas Gerais Laboratory of Hypertension Department of Physiology and BiophysicsInstitute of Biological SciencesFederal University of Minas Gerais Laboratory of Immunopharmacology Department of Biochemistry and ImmunologyInstitute of Biological SciencesFederal University of Minas Gerais

Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.

关键词： Hepatic fibrosis Renin angiotensin system Angiotensin II Angiotensin-(1-7) Receptor Mas Angiotensin converting enzyme 2

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Development of hepatorenal syndrome in bile duct ligated rats

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World Journal of Gastroenterology 2008年第28期14卷 4505-4511页

作者： Regina M Pereira Robson AS dos Santos Eduardo A Oliveira Virgínia HR Leite filipi LC dias Alysson S Rezende Lincoln P costa Lucíola S Barcelos Mauro M Teixeira Ana Cristina Sim■es e Silva Departamento de Ciências Biológicas Centro Universitário de Belo Horizonte-UNIBHAv.Mário WerneckBelo HorizonteMinas Gerais 30150-281Brazil Laboratório de Hipertenso Departamento de Fisiologia e BiofísicaInstituto de Ciências Biológicas (ICB)Universidade Federal de Minas Gerais (UFMG)Av.Antonio Carlos6627Belo HorizonteMinas Gerais 30150-281Brazil Departamento de Pediatria Faculdade de MedicinaUFMGAv.Alfredo Balena 190Belo HorizonteMinas Gerais 30150-281Brazil Departamento de Anatomia Patológica Faculdade de MedicinaUFMGAv.Alfredo Balena 190Belo HorizonteMinas Gerais 30150-281Brazil Laboratório de Imunofarmacologia Departamento de Bioquímica e ImunologiaICBUFMGAv.Antonio Carlos 6627Belo HorizonteMinas Gerais 30150-281Brazil

AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology. METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk). To determine renal function parameters, rats wereplaced in metabolic cages and, at the end of the experiment, blood and urine samples were obtained. Histology and hydroxyproline content were analyzed in liver and renal tissue. RESULTS: Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P = 0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including signif icant increase in serum creatinine and reductions in creatinine clearance, water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic f ibrosis according to post-procedure time was confirmed by histology. The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue. CONCLUSION: Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.

关键词： Hepatorenal syndrome Bile duct ligation Renal function Renin angiotensin system

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