Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/17373 |
Resumo: | Stroke occurs when blood flow to the brain is interrupted by an embolic or thrombotic occlusion of a cerebral artery (ischemic stroke) or by bleeding from a ruptured blood vessel (hemorrhagic stroke). Oxidative stress and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke, leading to apoptosis and cell death. Lipid accumulation may lead to progression of carotid plaques and inflammation, contributing to increased acute stroke risk. However, little is known about these events and markers in the late stroke (> 6 months) and if dyslipidemia could contribute to disease pathophysiology in a later phase. In this case-control study, we recruited stroke patients (n=40) and health subjects (control group; n=40). Dichlodihidrorofluorescin (DCFH), nitrite/nitrate (NOx), Tumor necrosis factor – alpha (TNF-α), Acetylcholinesterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) and Picogreen (PG) were measured in periphery blood samples. Furthermore, a correlation among all measured markers (DCFH, NOx, TNF-α, AChE, CASP 8, CASP 3 and PG) was realized. The markers levels were also compared to triglycerides (TG), total (CHO), LDL and HDL cholesterol levels and medications used. Statistical analyses showed that stroke patients presented an increase of DCFH, NOx, TNF-α and AChE levels when compared to control subjects. In addition, we observed that stroke patients had significantly higher CASP 8, CASP 3 and PG levels than control group. A significant correlation between TNF-α with CASP 8 (r = 0.4) and CASP 3 (r = 0.4) levels was observed, but not with oxidative/nitrosative markers. Moreover, we observed that stroke patients with dyslipidemia had significantly higher TNF-α, CASP 8 and CASP 3 levels than stroke without dyslipidemia and control groups. Our findings suggest that oxidative and inflammatory markers may be still increased and lead to caspases activation and DNA damage even after 6 months to cerebral injury. Furthermore, it is plausible to propose that dyslipidemia may contribute to worsen proinflammatory state in a later phase of stroke and an increased risk to new neurovascular events. |
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Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemiaInflamatory and apoptotic pathways association in a later phase of stroke pathophysiology: relation to dyslipidemiaAcidente vascular encefálicoEstresse oxidativoInflamaçãoCaspasesDano ao DNA e dislipidemiaStrokeOxidative stressInflammationCaspasesDNA damageDyslipidemiaCNPQ::CIENCIAS DA SAUDE::FARMACIAStroke occurs when blood flow to the brain is interrupted by an embolic or thrombotic occlusion of a cerebral artery (ischemic stroke) or by bleeding from a ruptured blood vessel (hemorrhagic stroke). Oxidative stress and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke, leading to apoptosis and cell death. Lipid accumulation may lead to progression of carotid plaques and inflammation, contributing to increased acute stroke risk. However, little is known about these events and markers in the late stroke (> 6 months) and if dyslipidemia could contribute to disease pathophysiology in a later phase. In this case-control study, we recruited stroke patients (n=40) and health subjects (control group; n=40). Dichlodihidrorofluorescin (DCFH), nitrite/nitrate (NOx), Tumor necrosis factor – alpha (TNF-α), Acetylcholinesterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) and Picogreen (PG) were measured in periphery blood samples. Furthermore, a correlation among all measured markers (DCFH, NOx, TNF-α, AChE, CASP 8, CASP 3 and PG) was realized. The markers levels were also compared to triglycerides (TG), total (CHO), LDL and HDL cholesterol levels and medications used. Statistical analyses showed that stroke patients presented an increase of DCFH, NOx, TNF-α and AChE levels when compared to control subjects. In addition, we observed that stroke patients had significantly higher CASP 8, CASP 3 and PG levels than control group. A significant correlation between TNF-α with CASP 8 (r = 0.4) and CASP 3 (r = 0.4) levels was observed, but not with oxidative/nitrosative markers. Moreover, we observed that stroke patients with dyslipidemia had significantly higher TNF-α, CASP 8 and CASP 3 levels than stroke without dyslipidemia and control groups. Our findings suggest that oxidative and inflammatory markers may be still increased and lead to caspases activation and DNA damage even after 6 months to cerebral injury. Furthermore, it is plausible to propose that dyslipidemia may contribute to worsen proinflammatory state in a later phase of stroke and an increased risk to new neurovascular events.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO Acidente Vascular Encefálico (AVE) é caracterizado pela perda rápida da função neurológica por uma isquemia ou hemorragia cerebral. No AVE isquêmico, o estresse oxidativo e a neuroinflamação contribuem para a patofisiologia do dano cerebral, conduzindo a apoptose e morte celular. A dislipidemia é considerada um dos principais fatores de risco para o desenvolvimento do AVE, induzindo a aterogênese e inflamação, aumentando as chance de novos eventos vasculares agudos. Entretanto, são escassos os estudos sobre estes eventos na fase tardia (>6 meses) do AVE e se a dislipidemia pode contribuir para a patofisiologia nesta fase da doença. O presente estudo teve como objetivo investigar se existe uma associação entre a via inflamatória e apoptótica, bem como, um envolvimento do dano oxidativo e da dislipidemia nas amostras sanguíneas de pacientes com AVE na fase tardia. Este foi um estudo caso-controle, onde 40 pacientes que sofreram AVE (Grupo AVE) e 40 sujeitos saudáveis (Grupo Controle) foram recrutados a realizar uma coleta de sangue e preenchimento de um questionário clínico. Foram mensurados os seguintes marcadores: Diclorodihidrofluorosceína (DCF), Nitrito/Nitrato (NOx), Fator de necrose tumoral alfa (TNF-α), Acetilcolinterterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) e Picogreen (PG), em amostras sanguíneas da circulação periférica. Além disso, foram realizadas correlações entre DCF, NOx, TNF-α, AChE, CASP 8, CASP 3 e PG com os grupos do estudo. Os níveis dos marcadores também foram comparados com indicadores de perfil lipídico como: triglicerídeos (TG), colesterol total (CT), LDL e HDL e o perfil medicamentoso. As análises estatísticas mostraram que os pacientes pós-AVE apresentaram níveis aumentados de DCF (p<0,0001), NOx (p<0,0001), TNF-α (p<0,0001) e AChE (p<0,0001), assim como, CASP 8 (p<0,0001), CASP 3 (p<0,0001) e PG (p<0,0001) quando comparados ao controle. Uma correlação positiva foi observada entre os níveis de TNF-α com a CASP 8 (r = 0,4 ; p<0,05) e CASP 3 (r = 0,4 ; p<0,05), porém quando comparado aos níveis oxidativos/nitrosativos não houve correlação. Além disso, o estudo mostrou que os pacientes pós-AVE dislipidêmicos (AVEd) apresentaram níveis significativamente elevados de TNF-α, CASP 8 e CASP 3, quando comparados com os pacientes pós-AVE sem dislipidemia (AVEnd) e com o grupo controle. Desta forma, os resultados sugerem que os marcadores oxidativos e inflamatórios podem estar aumentados mesmo na fase crônica do AVE, e culminarem na ativação das caspases (apoptose) e consequente dano ao DNA. Assim, é plausível propor que a dislipidemia na fase tardia do AVE pode contribuir para a piora do quadro inflamatório e aumentar o risco de novos eventos neurovasculares.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdeFighera, Michele Rechiahttp://lattes.cnpq.br/8583392747509231Santos, Adair Roberto Soares doshttp://lattes.cnpq.br/9263042062534666Stigger, Felipe de Souzahttp://lattes.cnpq.br/8472687293029599Pascotini, Eduardo Tanuri2019-07-09T21:50:22Z2019-07-09T21:50:22Z2015-01-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/17373porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2019-07-10T06:01:40Zoai:repositorio.ufsm.br:1/17373Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-07-10T06:01:40Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia Inflamatory and apoptotic pathways association in a later phase of stroke pathophysiology: relation to dyslipidemia |
title |
Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia |
spellingShingle |
Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia Pascotini, Eduardo Tanuri Acidente vascular encefálico Estresse oxidativo Inflamação Caspases Dano ao DNA e dislipidemia Stroke Oxidative stress Inflammation Caspases DNA damage Dyslipidemia CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia |
title_full |
Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia |
title_fullStr |
Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia |
title_full_unstemmed |
Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia |
title_sort |
Associação da via inflamatória e apoptótica na patofisiologia do acidente vascular encefálico tardio: relação com a dislipidemia |
author |
Pascotini, Eduardo Tanuri |
author_facet |
Pascotini, Eduardo Tanuri |
author_role |
author |
dc.contributor.none.fl_str_mv |
Fighera, Michele Rechia http://lattes.cnpq.br/8583392747509231 Santos, Adair Roberto Soares dos http://lattes.cnpq.br/9263042062534666 Stigger, Felipe de Souza http://lattes.cnpq.br/8472687293029599 |
dc.contributor.author.fl_str_mv |
Pascotini, Eduardo Tanuri |
dc.subject.por.fl_str_mv |
Acidente vascular encefálico Estresse oxidativo Inflamação Caspases Dano ao DNA e dislipidemia Stroke Oxidative stress Inflammation Caspases DNA damage Dyslipidemia CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Acidente vascular encefálico Estresse oxidativo Inflamação Caspases Dano ao DNA e dislipidemia Stroke Oxidative stress Inflammation Caspases DNA damage Dyslipidemia CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Stroke occurs when blood flow to the brain is interrupted by an embolic or thrombotic occlusion of a cerebral artery (ischemic stroke) or by bleeding from a ruptured blood vessel (hemorrhagic stroke). Oxidative stress and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke, leading to apoptosis and cell death. Lipid accumulation may lead to progression of carotid plaques and inflammation, contributing to increased acute stroke risk. However, little is known about these events and markers in the late stroke (> 6 months) and if dyslipidemia could contribute to disease pathophysiology in a later phase. In this case-control study, we recruited stroke patients (n=40) and health subjects (control group; n=40). Dichlodihidrorofluorescin (DCFH), nitrite/nitrate (NOx), Tumor necrosis factor – alpha (TNF-α), Acetylcholinesterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) and Picogreen (PG) were measured in periphery blood samples. Furthermore, a correlation among all measured markers (DCFH, NOx, TNF-α, AChE, CASP 8, CASP 3 and PG) was realized. The markers levels were also compared to triglycerides (TG), total (CHO), LDL and HDL cholesterol levels and medications used. Statistical analyses showed that stroke patients presented an increase of DCFH, NOx, TNF-α and AChE levels when compared to control subjects. In addition, we observed that stroke patients had significantly higher CASP 8, CASP 3 and PG levels than control group. A significant correlation between TNF-α with CASP 8 (r = 0.4) and CASP 3 (r = 0.4) levels was observed, but not with oxidative/nitrosative markers. Moreover, we observed that stroke patients with dyslipidemia had significantly higher TNF-α, CASP 8 and CASP 3 levels than stroke without dyslipidemia and control groups. Our findings suggest that oxidative and inflammatory markers may be still increased and lead to caspases activation and DNA damage even after 6 months to cerebral injury. Furthermore, it is plausible to propose that dyslipidemia may contribute to worsen proinflammatory state in a later phase of stroke and an increased risk to new neurovascular events. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-01-22 2019-07-09T21:50:22Z 2019-07-09T21:50:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/17373 |
url |
http://repositorio.ufsm.br/handle/1/17373 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805922129970987008 |