ABSTRACT
PURPOSE: To investigate if expression of genes encoding pro and anti-apoptotic proteins in the rat enteric endothelial cells stimulated by intestinal ischemia followed by reperfusion (IR) can be modified by treatment with heparin (HP). METHODS: Eighteen adult Wistar rats were divided in three groups: sham group submitted to laparotomy only (SG), ischemia followed by reperfusion group (IRG); ischemia followed by reperfusion plus pretreatment with HP 100 mg.kg-1 (IRG+HP). Ischemia was performed by clamping of the superior mesenteric artery. After 60 min of ischemia, metal clamps were removed for reperfusion for 120 min. Gene expression of encoding pro (Casp1, Casp6, Casp3, Cflar, Fas and Pgl) and anti-apoptotic (Bcl2, Bcl2l1 and Naip2) proteins in rat enteric endothelial cells was evaluated by PCR microarray method. RESULTS: Compared to rat endothelial cells of SG, the expression of pro-apoptotic genes was up-regulated in IRG while anti-apoptotic genes were down-regulated. In contrast, the expression of anti-apoptotic genes in IRG+HP was up-regulated while pro-apoptotic genes was down-regulated compared to SG. CONCLUSION: The attenuation by heparin of intestinal ischemia-reperfusion previously demonstrated in rodents could be related with ability of this drug to stimulate and reduce gene expression of encoding anti and pro-apoptotic proteins, respectively. .
Subject(s)
Animals , Male , Apoptosis Regulatory Proteins/drug effects , Endothelial Cells/drug effects , Gene Expression/drug effects , Heparin/pharmacology , Intestines/blood supply , Ischemia/drug therapy , Reperfusion Injury/drug therapy , Apoptosis Regulatory Proteins/genetics , Constriction , Down-Regulation , Endothelial Cells/pathology , Free Radical Scavengers/pharmacology , Intestines/pathology , Ischemia/pathology , Mesenteric Artery, Superior , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Reperfusion Injury/pathology , Time Factors , Treatment Outcome , Up-RegulationABSTRACT
PURPOSE: To investigate the effects of ischemic preconditioning (IPC) on the expression of pro and anti-apoptotic genes in rat endothelial cells undergoing enteric ischemia (I) and reperfusion (R). METHODS: Thirty rats underwent clamping of the superior mesenteric vessels. Sham group (GS) laparotomy only; Ischemia (GI): intestinal ischemia (60 min); Ischemia and Reperfusion (GIR): ischemia (60 min) and reperfusion (120 min); Ischemia and intestinal ischemic preconditioning (GI + IPC) : 5 minutes of ischemia followed by 10 min of reperfusion before sustained ischemia (60 min) ischemia and reperfusion and IPC (GIR + IPC): 5 min ischemia followed by 10 min of reperfusion before sustained ischemia (60min) and reperfusion (120 min). Rat Endothelial Cell Biology (PCR array) to determine the expression of genes related to endothelial cell biology. RESULTS: Gene expression of pro-apoptotic markers (Casp1, Casp6, Cflar, Fas, and Pgl) was down regulated in GI+IPC and in GIR + IPC. In contrast, the expression of anti-apoptotic genes (Bcl2 and Naip2), was up-regulated in GI + IPC and in GIR + IPC. CONCLUSION: Ischemic preconditioning may protect against cell death caused by ischemia and reperfusion.
Subject(s)
Animals , Male , Rats , Apoptosis/genetics , Endothelial Cells/physiology , Gene Expression/genetics , Intestines/blood supply , Ischemic Preconditioning/methods , Reperfusion Injury/genetics , Random Allocation , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Reperfusion Injury/prevention & control , Time FactorsABSTRACT
Objetivo: avaliar os resultados anatomopatológicos das peças operatórias de pacientes submetidas a cirurgia com alça de alta freqüência e sua relação com a localização colposcópica da atipia. Métodos: estudo retrospectivo de 134 pacientes que apresentavam neoplasia intra-epitelial ao exame citológico e/ou anatomopatológico e que foram submetidas a cirurgia com alça de alta freqüência. As pacientes foram separadas em três grupos, de acordo com a localização das atipias: Grupo I (n=36): pacientes com atipia localizada na ectocérvice e junção escamo-colunar visível; Grupo II (n=50): pacientes com atipia ecto-endocervical, e Grupo III (n=48): pacientes com colposcopia insatisfatória. Resultados: o Grupo I apresentou média de idade de 33, o Grupo II média de 39 e o Grupo Ill, 48 anos. O comprometimento das margens cirúrgicas por neoplasia ocorreu respectivamente em 8,3, 36 e 29,2 por cento dos casos quando avaliados por grupo. No acompanhamento das pacientes verificou-se que a porcentagem de doença residual foi de 4,2 por cento no Grupo I, 31,6 por cento no Grupo II e 35,5 por cento no Grupo III. Conclusão: pacientes com lesões localizadas no canal endocervical apresentaram maior taxa de margens comprometidas. Pacientes com neoplasia intra-epitelial de alto grau localizadas no canal endocervical e idade superior a 40 anos têm maior chance de apresentar margens comprometidas e doença residual, necessitando de controles citológicos e colposcópicos rigorosos.