Journal of hepatology · 2008
Down-regulation of genes related to the adrenergic system may contribute to splanchnic vasodilation in rat portal hypertension.
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Coll Mar, Genescà Joan, Raurell Imma, Rodríguez-Vilarrupla Aina, Mejías Marc, Otero Teresa, Oria Marc, Esteban Rafael, Guardia Jaime, Bosch Jaime, Martell María
Аннотация
BACKGROUND/AIMS: Splanchnic vasodilation initiates the hyperdynamic syndrome in portal hypertension. We aimed to explore molecular mechanisms involved in the development of mesenteric vasodilation in portal hypertension.
METHODS: Superior mesenteric artery (SMA) samples from portal vein ligated (PVL) and sham rats were compared in a time course experiment using DNA microarrays. Selected genes were quantified by qRT-PCR in PVL and cirrhotic rats. Inmunohistochemistry of tyrosine hydroxylase (Th) and norepinephrine was assessed in SMA sections of PVL and sham rats. Western blot analysis of Th, dopamine beta-hydroxylase (Dbh) and synaptosome-associated protein (Snap-25) was performed in SMA and jejunum samples from the animal models.
RESULTS: Fifty differentially expressed genes implicated in neurotransmission, especially adrenergic, were detected in SMA samples from PVL rats. Sequential analysis showed a profound down-regulation at 14 days in PVL rats. These down-regulated genes were confirmed by RT-PCR in SMA from PVL and cirrhotic rats. Th and NE detection by immunohistochemistry was reduced in PVL compared to sham. Th, Dbh and Snap-25 expression was lower in SMA from 14-day PVL and cirrhotic rats compared to sham and control rats, respectively.
CONCLUSIONS: Genetic down-regulation of genes related to the adrenergic system might have a role in splanchnic vasodilation of portal hypertension.
METHODS: Superior mesenteric artery (SMA) samples from portal vein ligated (PVL) and sham rats were compared in a time course experiment using DNA microarrays. Selected genes were quantified by qRT-PCR in PVL and cirrhotic rats. Inmunohistochemistry of tyrosine hydroxylase (Th) and norepinephrine was assessed in SMA sections of PVL and sham rats. Western blot analysis of Th, dopamine beta-hydroxylase (Dbh) and synaptosome-associated protein (Snap-25) was performed in SMA and jejunum samples from the animal models.
RESULTS: Fifty differentially expressed genes implicated in neurotransmission, especially adrenergic, were detected in SMA samples from PVL rats. Sequential analysis showed a profound down-regulation at 14 days in PVL rats. These down-regulated genes were confirmed by RT-PCR in SMA from PVL and cirrhotic rats. Th and NE detection by immunohistochemistry was reduced in PVL compared to sham. Th, Dbh and Snap-25 expression was lower in SMA from 14-day PVL and cirrhotic rats compared to sham and control rats, respectively.
CONCLUSIONS: Genetic down-regulation of genes related to the adrenergic system might have a role in splanchnic vasodilation of portal hypertension.
Предметные рубрики MeSH
AnimalsCarbon TetrachlorideDisease Models, AnimalDopamine beta-HydroxylaseDown-RegulationGene Expression ProfilingHypertension, PortalImmunohistochemistryLigationLiver CirrhosisMaleMesenteric Artery, SuperiorNorepinephrineOligonucleotide Array Sequence AnalysisPortal VeinRNA, MessengerRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionSplanchnic CirculationSynaptosomal-Associated Protein 25Tyrosine 3-MonooxygenaseVasodilation