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| 1 | Renin-angiotensin system in the pathogenesis of liver fibrosis显示文摘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)□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. | Regina Maria Pereira Robson Augusto Souza dos Santos Filipi Leles da Costa Dias Mauro Martins Teixeira Ana Cristina Simoes e Silva | 2009 | World Journal of Gastroenterology2009，15，21： | 37 |
| 2 | Current knowledge on esophageal atresia显示文摘Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is the most common congenital anomaly of the esophagus. The improvement of survival observed over the previous two decades is multifactorial and largely attributable to advances in neonatal intensive care, neonatal anesthesia, ventilatory and nutritional support, antibiotics, early surgical intervention, surgical materials and techniques. Indeed, mortality is currently limited to those cases with coexisting severe life-threatening anomalies. The diagnosis of EA is most commonly made during the first 24 h of life but may occur either antenatally or may be delayed. The primary surgical correction for EA and TEF is the best option in the absence of severe malformations. There is no ideal replacement for the esophagus and the optimal surgical treatment for patients with long-gap EA is still contro-versial. The primary complications during the postoperative period are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal dysmotility, fistula recurrence, respiratory disorders and deformities of the thoracic wall. Data regarding long-term outcomes and follow-ups are limited for patients following EA/TEF repair. The determination of the risk factors for the complicated evolution following EA/TEF repair may positively impact long-term prognoses. Much remains to be studied regarding this condition. This manuscript provides a literature review of the current knowledge regarding EA. | Paulo Fernando Martins Pinheiro Ana Cristina Simoes e Silva Regina Maria Pereira | 2012 | World Journal of Gastroenterology2012，18，28： | 35 |
| 3 | Renin angiotensin system in liver diseases: Friend or foe?显示文摘In the last three decades,the understanding of the renin angiotensin system(RAS)has been changed by the discoveries of functional local systems,novel biologically active peptides,additional specific receptors,alternative pathways of angiotensin(Ang)?Ⅱ?generation,and new roles for enzymes and precursor components other than those in Ang?Ⅱ?synthesis.In this regard,the discovery that Ang-(1-7)opposes the pressor,proliferative,pro-fibrotic,and pro-inflammatory effects mediated by Ang?Ⅱ?has contributed to the realization that the RAS is composed of two axes.The first axis consists of the angiotensin-converting enzyme(ACE),with Ang?Ⅱ?as the end product,and the angiotensin type 1(AT1)receptor as the main effector mediating the biological actions of Ang?Ⅱ.The second axis results from ACE2-mediated hydrolysis of Ang?Ⅱ,leading to the production of Ang-(1-7),with the Mas receptor as the main effector conveying the vasodilatory,antiproliferative,anti-fibrotic,and anti-inflammatory effects of Ang-(1-7).Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver diseases.In this manuscript,we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications,including hemodynamic changes and hepatorenal syndrome.The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed. | Ana Cristina Simoes e Silva Aline S Miranda Natália P Rocha Antonio L Teixeira | 2017 | World Journal of Gastroenterology2017，23，19： | 12 |
| 4 | Relationship between angiotensin-(1-7) and angiotensin Ⅱ correlates with hemodynamic changes in human liver cirrhosis显示文摘AIM:To measure circulating angiotensins at different stages ofhuman cirrhosis and to further evaluate a possible relationship between renin angiotensin system (RAS) components and hemodynamic changes.METHODS: Patients were allocated into 4 groups: mild-to-moderate liver disease (MLD), advanced liver disease (ALD), patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity (PRA), angiotensin (Ang) , Ang Ⅱ, and Ang-(1-7) levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components.RESULTS: PRA and angiotensins were elevated in ALD when compared to MLD and controls (P < 0.05). In contrast, Ang was signicantly reduced in MLD. Ang-(1-7)/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-(1-7)/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation (0.52 ± 0.08 vs 0.38 ± 0.04, P < 0.02), whereas the peripheral circulating Ang /Ang ratio was elevated in comparison to splanchnic lev-els (0.18 ± 0.02 vs 0.13 ± 0.02, P < 0.04). Ang-(1-7)/Ang Ⅱ ratios positively correlated with cardiac output (r= 0.66) and negatively correlated with systemic vascular resistance (r =-0.70).CONCLUSION: Our ndings suggest that the relation-ship between Ang-(1-7) and Ang Ⅱmay play a role in the hemodynamic changes ofhuman cirrhosis. | Walkíria Wingester Vilas-Boas Antnio Ribeiro-Oliveira Jr Regina Maria Pereira Renata da Cunha Ribeiro Jerusa Almeida Ana Paula Nadu Ana Cristina Simoes e Silva Robson Augusto Souza dos Santos | 2009 | World Journal of Gastroenterology2009，15，20： | 11 |
| 5 | Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy:A single center report of 8 cases显示文摘This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics. | Susana Rodrigues Susana Lopes Fernando Magro Hélder Cardoso Ana Maria Horta e Vale Margarida Marques Eva Mariz Miguel Bernardes Joanne Lopes Fátima Carneiro Guilherme Macedo | 2015 | World Journal of Gastroenterology2015，21，24： | 9 |
| 6 | Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases显示文摘Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes. | Ana Paula Oppenheimer Christopher Koh Mary McLaughlin John C Williamson Thomas D Norton Jennifer Laudadio Theo Heller David E Kleiner Kevin P High Caryn G Morse | 2013 | World Journal of Gastroenterology2013，19，1： | 8 |
| 7 | Celiac disease serology in patients with different pretest probabilities: Is biopsy avoidable?显示文摘AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential se- rological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects. | Emilia Sugai María L Moreno Hui J Hwang Ana Cabanne Adriana Crivelli Fabio Nach-man Horacio Vázquez Sonia Niveloni Julio Argonz Roberto Mazure Graciela La Motta María E Caniggia Edgardo Smecuol Néstor Chopita Juan C Gómez Eduardo Maurińo Julio C Bai | 2010 | World Journal of Gastroenterology2010，16，25： | 4 |
| 8 | Hepatic encephalopathy:Lessons from preclinical studies显示文摘Hepatic encephalopathy(HE) is a major complication that is closely related to the progression of end-stage liver disease.Metabolic changes in advanced liver failure can promote cognition impairment,attention deficits and motor dysfunction that may result in coma and death.HE can be subdivided according to the type of hepatic injury,namely,type A,which results from acute liver failure,type B,which is associated with a portosystemic shunting without intrinsic liver disease,and type C,which is due to chronic liver disease.Several studies have investigated the pathogenesis of the disease,and most of the mechanisms have been explored using animal models.This article aimed to review the use of preclinical models to investigate HE.The most used animal species are rats and mice.Experimental models of type A HE include surgical procedures and the administration of hepatotoxic medications,whereas models of types B and C HE are generally surgically induced lesions in liver tissue,which evolve to hepatic cirrhosis.Preclinical models have allowed the comprehension of the pathways related to HE. | Luiza Cioglia Dias Lima Aline Silva Miranda Rodrigo Novaes Ferreira Milene Alvarenga Rachid Ana Cristina Sim?es e Silva | 2019 | World Journal of Hepatology2019，11，2： | 4 |
| 9 | Autoimmune hepatitis in childhood: The role of genetic and immune factors显示文摘Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population. | Priscila Menezes Ferri Liu Débora Marques de Miranda Eleonora Druve Tavares Fagundes Alexandre Rodrigues Ferreira Ana Cristina Simoes e Silva | 2013 | World Journal of Gastroenterology2013，19，28： | 3 |
| 10 | Intravenous immune globulin suppresses angiogenesis in mice and humans显示文摘Human intravenous immune globulin(IVIg),a purified IgG fraction composed of~60%IgG1 and obtained from the pooled plasma of thousands of donors,is clinically used for a wide range of diseases.The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG(IgG)Fc regions.Recently,we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI,a high-affinity receptor for IgG1.Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases,namely,neovascular age-related macular degeneration,corneal neovascularization,colorectal cancer,fibrosarcoma and peripheral arterial ischemic disease.Angioinhibition was mediated by the Fc region of IVIg,required FcγRI and had similar potency in transgenic mice expressing human FcγRs.Finally,IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities.These data place IVIg,an agent approved by the US Food and Drug Administration,as a novel angioinhibitory drug in doses that are currently administered in the clinical setting.In addition,they raise the possibility of an unintended effect of IVIg on blood vessels. | Reo Yasuma Valeria Cicatiello Takeshi Mizutani Laura Tudisco Younghee Kim Valeria Tarallo Sasha Bogdanovich Yoshio Hirano Nagaraj Kerur Shengjian Li Tetsuhiro Yasuma Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Balamurali K Ambati Sevim Barbasso Helmers Ingrid E Lundberg Ondrej Viklicky Jeanette HW Leusen J Sjef Verbeek Bradley D Gelfand Ana Bastos-Carvalho Sandro De Falco Jayakrishna Ambati | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 3 |
| 11 | Association of Helicobacter pylori infection and giardiasis: Results from a study of surrogate markers for fecal exposure among children显示文摘AIM: To investigate whether Helicobacter pylori (H pykori)infection is associated with hepatitis A virus (HAV) infection, presence of enteroparasites, and other surrogates of fecal exposure.METHODS: We conducted a cross-sectional study in 121 children consecutively admitted at a pediatric hospital inSalvador, Brazil.H pylori and HAV infection were identified by the presence of serum antibodies. Stool specimens were examined for the presence of ova and parasites. A structured questionnaire inquiring about sanitary conditions and life style was applied to each subject. RESULTS: Fifty-one of the 121 children (42.1%) werefound to be seropositive for H pylori, and 45 (37.2%) for HAV. The seroprevalence ofHpyloriand HAV both increased significantly with age. Cross-tabulation of data showed that 26 (21.5%) were seropositive and 51 (42.1%) were negative for bothHpyloriand HAV antibodies (χ2 = 7.18,OR = 2.8, CI 1.30-5.97). The age adjusted OR for an HAV-infected child being H pylori positive was 2.3 (CI1.02-5.03). The agreement between H pylori and HAVseropositivity was fair (κ = 0.24). After controlling for possible confounding, the variables remaining independently associated with seropositivity to H pyloriwere age,presence of Giardia lamblia in feces (OR = 3.2, 95%CI, 1.1-9.5) and poor garbage disposal quality (OR = 2.4,95%CI, 1.1-5.1).CONCLUSION: Our data suggest that H pylori infection is associated with surrogate markers of fecal exposure. Thus, we conclude that the fecal-oral route is relevant in the transmission of HP among children in an urban setting of a developing country. The association observed between G. lamblia and H pylori infection may have several explanations. Further studies to investigate this relationship are warranted. | Edson Duarte Moreira Jr Victor Bastos Nassri Rafaela Sousa Santos Junísia Ferraz Matos Wilson Andrade de Carvalho Célia Stolve Silvani Círia Santana e Sant'Ana | 2005 | World Journal of Gastroenterology2005，11，18： | 3 |
| 12 | Diagnostic criteria for autoimmune hepatitis in children: A challenge for pediatric hepatologists显示文摘Autoimmune hepatitis (AIH) is a progressive inflammatory liver disorder that is rare in children and adolescents. AIH has a broad clinical spectrum and a quick response to treatment with corticosteroids and immunosuppressive medication. The available diagnosis criteria have limitations and should be evaluated in pediatric populations. Recently, some studies reported that the 2008 simplified diagnostic criteria for AIH could be used in children with high sensibility and specificity. In addition, the authors reported that globulin and immunoglobulin G levels can be used interchangeably for diagnostic purposes. They also demonstrated that the 2008 simplified criteria fail in identifying patients with fulminant hepatic failure. Here, we discuss the limitations of the use of these criteria in pediatric patients and the requirement of more studies to improve the diagnosis of AIH in children. | Priscila Menezes Ferri Alexandre Rodrigues Ferreira Débora Marques Miranda Ana Cristina Sim■es e Silva | 2012 | World Journal of Gastroenterology2012，18，33： | 3 |
| 13 | Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis显示文摘The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis. | Aline Silva Miranda Ana Cristina Sim?es e Silva | 2017 | World Journal of Gastroenterology2017，23，48： | 2 |
| 14 | Management of autoimmune hepatitis:Focus on pharmacologic treatments beyond corticosteroids显示文摘In autoimmune hepatitis, patients who are intolerant or with toxicity experience, non-responders, relapsers or refractory are challenging. Non-standard drugs are being tried to preemptively avoid corticosteroid-related side effects. Prognosis and quality of life of life rely on treatment optimization. Recently, emergence of powerful immunosuppressive agents, mainly from liver transplantation, challenged the supremacy of the corticosteroid regime and promise greater immunosuppression than conventional medications, offer site-specific actions and satisfactory patient tolerance. Successes in experimental models of related diseases have primed these molecular interventions. We performed a literature review on alternative treatments. Azatioprine intolerance is the principal indication for mycophenolate use butit can be used as a front-line therapy. Cyclosporine A and tacrolimus have been tested for non-responders or relapsers. Rituximab may be used as salvage therapy. Anti-tumor necrosis factor-alpha agents may be used for incomplete responses or non-responders. Methotrexate is possibly an alternative for induction of remission and maintenance in refractory patients. Cyclophosphamide has been included in the induction regimen with corticosteroids. Ursodeoxycholic acid action is mainly immunomodulatory. Non-standard treatments are coming slowly to the attention, but its use should be cautious performed by experienced centers. | Marta Casal Moura Rodrigo Liberal Hélder Cardoso Ana Maria Horta e Vale Guilherme Macedo | 2014 | World Journal of Hepatology2014，6，6： | 2 |
| 15 | Human papillomavirus and cervical cancer显示文摘 | Mark Schiffman Philip E Castle Jose Jeronimo Ana C Rodriguez Sholom Wacholder | 2007 | 2007 (9590)2007，，9590： | 2 |
| 16 | Hydrotherapy Versus Conventional Land-Based Exercise for the Management of Patients With Osteoarthritis of the Knee: A Randomized Clinical Trial显示文摘 | Silva Luciana E Valim Valeria Pessanha Ana Paula C Oliveira Leda M Myamoto Samira Jones Anamaria Natour Jamil | 2008 | Physical Therapy2008，，1： | 2 |
| 17 | Human papillomavirus and cervical cancer显示文摘 | Mark Schiffman Philip E Castle Jose Jeronimo Ana C Rodriguez Sholom Wacholder | 2007 | The Lancet . 2007 (9590)2007，，9590： | 2 |
| 18 | Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients显示文摘AIM:To evaluate the effect of β-blockade on angiotensins in the splanchnic and peripheral circulation of cirrhotic patients and also to compare hemodynamic parameters during liver transplantation according to propranolol pre-treatment or not. METHODS:Patients were allocated into two groups:outpatients with advanced liver disease(LD) and during liver transplantation(LT). Both groups were subdivided according to treatment with propranolol or not. Plasma was collected through peripheral venipuncture to determine plasma renin activity(PRA),Angiotensin(Ang) Ⅰ,Ang Ⅱ,and Ang-(1-7) levels by radioimmunoassay in LD group. During liver transplantation,hemodynamic parameters were determined and blood samples were obtained from the portal vein to measure renin angiotensin system(RAS) components.RESULTS:PRA,Ang Ⅰ,Ang Ⅱ and Ang-(1-7) were signifi cantly lower in the portal vein and periphery in all subgroups treated with propranolol as compared to non-treated. The relationships between Ang-(1-7) and Ang Ⅰ levels and between Ang Ⅱ and Ang Ⅰ were significantly increased in LD group receiving propranolol. The ratio between Ang-(1-7) and Ang Ⅱ remained unchanged in splanchnic and peripheral circulation in patients under β-blockade,whereas the relationship between Ang Ⅱ and Ang Ⅰ was significantly increased in splanchnic circulation of LT patients treated with propranolol. During liver transplantation,cardiac output and index as well systemic vascular resistance and index were reduced in propranolol-treated subgroup. CONCLUSION:In LD group,propranolol treatment reduced RAS mediators,but did not change the ratio between Ang-(1-7) and Ang Ⅱ in splanchnic and peripheral circulation. Furthermore,the modification of hemodynamic parameters in propranolol treated patients was not associated with changes in the angiotensin ratio. | Walkíria Wingester Vilas-Boas Antnio Ribeiro-Oliveira Jr Renata da Cunha Ribeiro Renata Lúcia Pereira Vieira Jerusa Almeida Ana Paula Nadu Ana Cristina Sim■es e Silva Robson Augusto Souza Santos | 2008 | World Journal of Gastroenterology2008，14，44： | 2 |
| 19 | Autophagy regulates adipose mass and differentiation in mice显示文摘 | Singh Rajat Xiang Youqing Wang Yongjun Baikati Kiran Cuervo Ana Maria Luu Yen K Tang Yan Pessin Jeffrey E Schwartz Gary J Czaja Mark J | 2009 | Journal of Clinical Investigation2009，，11： | 2 |
| 20 | Development of hepatorenal syndrome in bile duct ligated rats显示文摘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. | 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 | 2008 | World Journal of Gastroenterology2008，14，28： | 2 |
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