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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2017.tde-06012017-102934
Document
Author
Full name
Nathalia Butschkau Palazzin Yodono
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2016
Supervisor
Committee
Ramos, Simone Gusmão (President)
Faccioli, Lucia Helena
Garcia, Sergio Britto
 
Title in Portuguese
Análise das alterações na musculatura duodenal e resposta do hospedeiro contra infecção pelo Strongyloides venezuelensis e tratamento com Dexametasona: o papel da via JAK-STAT 6
Keywords in Portuguese
Dexametasona
Intestino delgado
Músculo liso
STAT
Strongyloides venezuelensis
Abstract in Portuguese
A estrongiloidíase é uma parasitose intestinal sendo considerada a quarta maior causada por nematódeos. O mecanismo de defesa contra a estrongiloidíase é mediada pela ativação de células de perfil Th2, que amplificam a resposta celular através da secreção de mediadores inflamatórios. O que faz da estrongiloidíase um grave problema de saúde pública, é o desenvolvimento da hiperinfecção, principalmente devido ao uso de glicocorticóides, onde ocorre aumento do número de larvas e fêmeas que se disseminam por todo organismo. Estudos demonstraram que algumas infecções helmínticas têm sido acompanhadas por hipertrofia e hipercontratillidade da musculatura intestinal, via JAK-STAT 6. Entretanto pouco se sabe sobre a influência desta via nas alterações da parede muscular do duodeno durante infecção pelo Strongyloides venezuelensis. O presente trabalho objetivou investigar as alterações morfológicas, imunológicas e patológicas da musculatura lisa intestinal que ocorrem em decorrência da infecção experimental pelo S. venezuelensis, bem como a interferência do tratamento com Dexametasona e o papel da via JAK - STAT 6 neste processo. Ratos Wistar foram inoculados com larvas de S. venezuelensis, tratados com dexametasona e sacrificados nos dias 5, 7, 14 e 21. Foram realizadas diversas colorações com a finalidade de quantificar as fêmeas adultas no duodeno, realizar morfometria da musculatura duodenal, quantificar eosinófilos e células caliciformes. Foi realizada análise da expressão gênica do gene STAT 6. Nossos resultados mostraram hiperplasia das células caliciformes, infiltrado eosinofílico e espessamento da musculatura lisa duodenal. Houve aumento na expressão de STAT 6 nos animais infectados. O tratamento com a Dexametasona inibiu drasticamente estas alterações. Entretanto o número de parasitas foi significativamente maior nos ratos infectados tratados quando comparados aos infectados. As alterações intestinais durante a infecção ocorreram na tentativa de expulsar o parasita e resolução da infecção. Contudo, a inibição deste processo provocada pela Dexametasona possivelmente retardou ou impediu a resolução da infecção.
 
Title in English
Analysis of changes in the duodenal musculature and host response to infection venezuelensis Strongyloides and Dexamethasone treatment: the role of the JAK-STAT 6
Keywords in English
Dexamethasone
Small intestine
Smooth muscle
STAT
Strongyloides venezuelensis
Abstract in English
Strongyloidiasis is an intestinal parasitosis with an obligatory pulmonary cycle, which represents the fourth largest parasitosis caused by nematodes. The mechanism of defense against strongyloidiasis is mediated by activation of Th2 cells, which amplify the cellular response through the secretion of inflammatory mediators. Strongyloidiasis is a serious public health problem due the development of hyperinfection, due to the use of glucocorticoids, where the number of worms and females increases, and disseminate to other organs. Studies have shown that some helminth infections have been accompanied by hypertrophy of intestinal muscles and hypercontractility, JAK-STAT 6 pathway. However little has been reported about on the influence of JAK-STAT 6 pathway in changes of the muscular wall of the duodenum during Strongyloides venezuelensis infection. The aim of this study was to identify the morphological, immunological and pathological changes of the intestinal smooth muscle during Strongyloides venezuelensis in Wistar rats and to determine the effects of Dexamethasone treatment and role of JAK-STAT 6 pathway in these process. Wistar rats were inoculated with S. venezuelensis larvae, treated with dexamethasone and killed at 5, 7, 14 and 21 days. Morphological and morphometric analyzes with routine stains to quantify globet cells, eosinophils and measure the circular and longitudinal layers of duodenal smooth muscle. Performed gene expression analysis of STAT 6. Goblet cell hyperplasia and increased of intestine smooth muscle wall thickness and eosinophils levels were elevated throughout the course of the infection. Moreover, an increase in the expression of STAT 6 in infected animals. The morphological findings and the immunomodulatory response to the infection were drastically reduced in dexamethasone-treated rats. However, the number of worms was significantly higher on infected and treated rats with Dexamethasone compared to just infected ones. The intestinal changes during infection ocurred in an attempt of expel the parasite and elucidate the infection. Although, the inhibition of the process caused by Dexamethasone possibly delay or prevent the resolution of infection
 
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Publishing Date
2017-04-19
 
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