RESUMEN
Abstract Purpose: To establish a hypotensive brain death pig model and observe the effects of hypotension on small bowel donors. Methods: The hypotensive brain death model was produced using the modified intracranial water sac inflation method in ten domestic crossbred pigs. Effects of hypotensive brain death on small bowel tissue morphology were evaluated through changes in intestinal tissue pathology, tight junction protein of the intestinal mucosa and plasma intestinal fatty acid-binding protein (i-FABP) levels. The pathophysiological mechanism was examined based on changes in superior mesenteric artery (SMA) blood flow and systemic hemodynamics. Results: After model establishment, SMA blood flow, and the mean arterial pressure (MAP) significantly decreased, while heart rate increased rapidly and fluctuated significantly. Small bowel tissue morphology and levels of tight junction protein of the intestinal mucosa showed that after model establishment, small bowel tissue injury was gradually aggravated over time (P<0.05). Plasma i-FABP levels significantly increased after brain death (P<0.05). Conclusions: A hypotensive brain death pig model was successfully established using an improved intracranial water sac inflation method. This method offers a possibility of describing the injury mechanisms more clearly during and after brain death.
Asunto(s)
Animales , Masculino , Femenino , Muerte Encefálica/fisiopatología , Modelos Animales de Enfermedad , Hipotensión/fisiopatología , Intestino Delgado/patología , Intestino Delgado/trasplante , Porcinos , Factores de Tiempo , Biopsia , Ensayo de Inmunoadsorción Enzimática , Western Blotting , Reproducibilidad de los Resultados , Microscopía Electrónica de Transmisión , Proteínas de Unión a Ácidos Grasos/sangre , Proteína de la Zonula Occludens-1/análisis , Hemodinámica , Intestino Delgado/irrigación sanguíneaRESUMEN
Matrix metalloproteinases-9 (MMP-9) is an important cancer-associated, zinc-dependent endopeptidase. To investigate the natural selection hypothesis of MMP-9, the orthologous sequences from 12 vertebrates were compared and a molecular evolution analysis was performed. Results suggest that amino acid residues present in the middle region of the protein are more selectively constrained, whereas amino acid residues in the C-terminal region of the MMP-9 protein including exon 13 showed lowest conservation level in non-primate species, suggesting that it is an exon with fast evolving rate compared to the others analyzed. InterProScan analysis shows that exon 13 was located in hemopexin (PEX) domain of MMP-9. Positive selection was detected in PEX domain of MMP-9 protein between human and other species, which indicates that selective pressure may play a role in shaping the function of MMP-9 in the course of evolution.