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Daniella Bonaventurahttp://lattes.cnpq.br/9290907947235226Steyner de França CôrtesLuciano dos Santos Aggum Capettinihttp://lattes.cnpq.br/7599902693349016Naiara de Assis Rabelo Ribeiro2021-02-24T17:05:02Z2021-02-24T17:05:02Z2020-12-04http://hdl.handle.net/1843/35058O tecido adiposo perivascular (PVAT) reveste a camada adventícia e envolve a maioria dos vasos sanguíneos. O PVAT libera moléculas biologicamente ativas que regulam o tônus vascular. Sabendo da importância desse tecido no controle do tônus vascular e que a hipotensão sistêmica, gerada em um quadro de sepse, é a principal causa de morte, o objetivo desse trabalho foi estudar os efeitos vasoativos e inflamatórios do PVAT na hiporreatividade aórtica induzida por sepse aguda. Para tanto, utilizou-se camundongos Balb/c machos (8 semanas), que foram divididos em dois grupos: sham e séptico. No grupo séptico, a sepse foi induzida por ligadura e perfuração transversal do ceco com agulha 26G. No grupo sham, a etapa de perfuração transversal do ceco não foi realizada. 6 horas após a indução da sepse, o papel do PVAT no tônus vascular foi avaliado em aortas torácicas dos grupos sham e séptico. Nossos resultados demonstram que apesar dos grupos sham e séptico apresentarem 100% de sobrevida, o grupo séptico apresentou leucopenia marcada por neutropenia, hipotermia, hipotensão arterial e alta pontuação de escore clínico quando comparado ao grupo sham. A vasoconstrição induzida por fenilefrina foi significativamente reduzida no grupo séptico em comparação ao grupo sham na ausência de PVAT. Entretanto, na presença do PVAT, o prejuízo na contratilidade vascular observado no grupo séptico foi reestabelecido. Ou seja, o PVAT apresentou um perfil vasoconstritor, se contrapondo a hiporreatividade causada pela sepse. Entre os mecanismos envolvidos nesse processo, sugerimos uma regulação recíproca entre espécies reativas de oxigênio, neste caso, ânion superóxido, gerado provavelmente a partir do complexo NADPH oxidase, e que por uma cascata de autoperpetuação, a COX-2 e seus derivados vasocontráteis, como tromboxano A2 e prostaglandina F2α também atuam “alimentando” essa via. Portanto sugerimos que o perfil contrátil apresentado pelo PVAT na sepse aguda (6h) se deva principalmente à participação de ânions superóxido, além de derivados da COX-2 e que ambos “autoalimentam” o ciclo favorecendo a contração observada.Perivascular adipose tissue (PVAT) lines the adventitial layer and surrounds most blood vessels. PVAT releases biologically active molecules that regulate vascular tone. Knowing the importance of this tissue in the control of vascular tone and that the systemic hypotension, generated in a case of sepsis, is the main cause of death, this study aimed to study the vasoactive and inflammatory effects of PVAT on aortic hyporeactivity induced by acute sepsis. For this purpose, male Balb / c mice (8 weeks) were used, which were divided into two groups: sham and septic. In the septic group, sepsis was induced by ligation and transverse perforation of the cecum with a 26G needle. In the sham group, the transverse perforation step of the cecum was not performed. 6 hours after sepsis induction, the role of PVAT in vascular tone was assessed in thoracic aortas of the sham and septic groups. Our results demonstrate that although the sham and septic groups have 100% survival, the septic group presented leukopenia marked by neutropenia, hypothermia, arterial hypotension, and a high clinical score when compared to the sham group. Phenylephrine-induced vasoconstriction was significantly reduced in the septic group compared to the sham group in the absence of PVAT. However, in the presence of PVAT, the impairment of vascular contractility observed in the septic group was reestablished. In other words, PVAT presented a vasoconstrictor profile, in contrast to the hyporeactivity caused by sepsis. Among the mechanisms involved in this process, we suggest a reciprocal regulation between reactive oxygen species, in this case, superoxide anion, probably generated from the NADPH oxidase complex, and that by a self-perpetuating cascade, COX-2 and its vasocontractable derivatives, as thromboxane A2 and prostaglandin F2α also act "feeding" this pathway. Therefore, we suggest that the contractile profile presented by PVAT in acute sepsis (6h) is mainly due to the participation of superoxide anions, in addition to derivatives of COX-2 and that both “feed” the cycle favoring the observed contraction.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências Biológicas - Fisiologia e FarmacologiaUFMGBrasilICB - DEPARTAMENTO DE FARMACOLOGIATecido adiposoVasos sanguíneosAortaSepseCiclo-oxigenase 2Estresse oxidativoPVATSepseHiporreatividadeCOXEstresse oxidativoCaracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse agudainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALDissertação Naiara Assis - Final -pdfa.pdfDissertação Naiara Assis - Final -pdfa.pdfapplication/pdf2158300https://repositorio.ufmg.br/bitstream/1843/35058/1/Disserta%c3%a7%c3%a3o%20Naiara%20Assis%20-%20Final%20-pdfa.pdf48dc3f620e66d1670b2612007f6a0068MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82119https://repositorio.ufmg.br/bitstream/1843/35058/2/license.txt34badce4be7e31e3adb4575ae96af679MD521843/350582021-02-24 14:05:02.627oai:repositorio.ufmg.br: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Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2021-02-24T17:05:02Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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