Estudo da lesão de isquemia e reperfusão hepática com e sem obstrução da via biliar e a modulação pela N-acetilcisteína e pelo precondicionamento isquêmico em ratos
Data
2004-09
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O objetivo foi estudar os efeitos do precondicionamento isquêmico e da N-acetilcisteína no
clampeamento da tríade portal comparado com o clampeamento vascular excluindo a via
biliar. Foram utilizados oitenta ratos EPM-1 Wistar distribuídos aleatoriamente em 2 grupos
de 40 animais. Estes se distinguiram pela inclusão (CVB=1) ou não (SVB=2) do ducto biliar
no clampeamento e foram redistribuídos em subgrupos de 10. IR1: 20 minutos após a
celiotomia, o pedículo contendo os elementos vasculares e o ducto biliar para os lobos
mediano e lateral esquerdo do fígado foi clampeado por 40 minutos, seguido de 30 minutos de
reperfusão; PCI1: 10 minutos de isquemia e 10 minutos de reperfusão. Após o PCI, seguiu-se
o mesmo procedimento usado para IR1; NAC1: (150mg.Kg-1
), administrada 15 minutos antes
do período isquêmico e 5 minutos antes da reperfusão; S1: dissecção e clampeamento
exclusivo do ducto biliar durante o período de isquemia. Nos subgrupos IR2, PCI2 e NAC2,
o clampeamento excluiu a via biliar; S2: dissecção e observação por 90min. Foram colhidas
amostras de sangue para a dosagem dos níveis enzimáticos e fragmento do fígado isquêmico
para coloração HE. Na análise estatística dos resultados foram utilizados testes não
paramétricos e o nível de rejeição da hipótese de nulidade foi fixado em 5%. A lesão de IR
hepática foi menos grave nos animais do grupo de clampeamento seletivo incluindo o ducto
biliar, com AST (766 vs 1380) e ALT (840 vs 1576); PCI protegeu o fígado da IR nos animais
com clampeamento seletivo da tríade portal com relação à AST (421 vs 1131) e ALT (315 vs
1085). Na avaliação morfológica, o PCI inibiu a ocorrência de esteatose microvesicular e
núcleos picnóticos (0% de lesão moderada ou intensa) e a NAC protegeu parcialmente 17% e
50% de lesão moderada ou intensa para CVB e SVB, respectivamente. O clampeamento
seletivo da tríade portal resulta em lesão de IR do fígado menos grave, quando comparado à
exclusão do ducto biliar. O PCI protege o fígado da lesão de IR. A NAC mostra um efeito de
proteção parcial, reduzindo as alterações parenquimatosas, mas não os níveis de
aminotransferases.
The aim of this study was to evaluate the effects of N-acetylcysteine and ischemic preconditioning on the portal triad clamping compared to arterial and portal clamping alone. 80 EPM-1 Wistar rats, were randomly separated in two groups of 40 animals. These groups were distinguished by the inclusion (CVB=1) or not (SVB=2) of the bile duct in the clamping, and the animals were allocated in your groups of to each IR 1: 20 minutes after celiotomy, the pedicle containing vascular elements and bile duct to the left lateral and median liver lobes were occluded for 40 minutes, followed by 30 minutes of reperfusion; PCI 1: ten minutes of ischemia and ten minutes of reperfusion. After PCI, the same as for IR 1 was done; NAC 1: (150mg.Kg-1 ) administrated 15 minutes prior to the ischemic period and 5 minutes prior to the reperfusion; SHAM 1: dissection and, just bile duct occlusion during the ischemic period; in the IR 2, PCI 2, and NAC 2 groups, the ischemia was achieved with an exclusive vascular occlusion. SHAM 2: dissection and observation for 90minutes. The blood was sampled for liver enzymes levels determination and ischemic liver samples were processed for HE stain. Statistical analysis was done (P 0.05). Hepatic IR injury were less severe for animals from the selective portal triad clamping group, with regard to AST (766 vs. 1380) and ALT (840 vs. 1576); PCI was able to protect the liver from IR injury for animals from the selective portal triad clamping group, with regard to AST (421 vs. 1131) and ALT (315 vs. 1085). In the morphological evaluation, PCI inhibited the microvesicular steatosis and picnotic nuclei (0% of moderate and severe injury), and NAC protected partially (17% and 50% of moderate and severe injury for CVB and SVB, respectively. Selective portal triad clamping results in a less severe hepatic IR injury, when compared to bile duct exclusion. PCI protects the liver from IR injury. NAC show a protective effect reducing parenchymal alterations, but not aminotransferase levels.
The aim of this study was to evaluate the effects of N-acetylcysteine and ischemic preconditioning on the portal triad clamping compared to arterial and portal clamping alone. 80 EPM-1 Wistar rats, were randomly separated in two groups of 40 animals. These groups were distinguished by the inclusion (CVB=1) or not (SVB=2) of the bile duct in the clamping, and the animals were allocated in your groups of to each IR 1: 20 minutes after celiotomy, the pedicle containing vascular elements and bile duct to the left lateral and median liver lobes were occluded for 40 minutes, followed by 30 minutes of reperfusion; PCI 1: ten minutes of ischemia and ten minutes of reperfusion. After PCI, the same as for IR 1 was done; NAC 1: (150mg.Kg-1 ) administrated 15 minutes prior to the ischemic period and 5 minutes prior to the reperfusion; SHAM 1: dissection and, just bile duct occlusion during the ischemic period; in the IR 2, PCI 2, and NAC 2 groups, the ischemia was achieved with an exclusive vascular occlusion. SHAM 2: dissection and observation for 90minutes. The blood was sampled for liver enzymes levels determination and ischemic liver samples were processed for HE stain. Statistical analysis was done (P 0.05). Hepatic IR injury were less severe for animals from the selective portal triad clamping group, with regard to AST (766 vs. 1380) and ALT (840 vs. 1576); PCI was able to protect the liver from IR injury for animals from the selective portal triad clamping group, with regard to AST (421 vs. 1131) and ALT (315 vs. 1085). In the morphological evaluation, PCI inhibited the microvesicular steatosis and picnotic nuclei (0% of moderate and severe injury), and NAC protected partially (17% and 50% of moderate and severe injury for CVB and SVB, respectively. Selective portal triad clamping results in a less severe hepatic IR injury, when compared to bile duct exclusion. PCI protects the liver from IR injury. NAC show a protective effect reducing parenchymal alterations, but not aminotransferase levels.