RESUMEN
BACKGROUND: Ischemia and reperfusion (I/R) injury is one of the main lesions after liver transplantation. This study aims to detect hypoxia-induced HIF-1α protects transplanted liver against I/R injury by promoting glucose metabolism to decrease mitochondrial injury and apoptosis on rat model. METHODS: The rats were given a treatment of 90 min non-lethal hypoxic preconditioning to induce and increase the HIF-1α expression. The autologous orthotopic liver transplantation model was used to imitate liver I/R injury. RESULTS: Hypoxic-induced HIF-1α was detected to increase in liver tissue after 90-minute hypoxic environment (HP vs. Ctrl, *P<0.001). After operation, the expression of HIF-1α in liver tissue was also stayed at a high level. At 24h after operation, several genes were promoted, such as the levels of HK-2 (HP vs. AT, 24h, *P=0.004), Lactate dehydrogenase (LDHA) (HP vs. AT, 24h, *P=0.003), pyruvate dehydrogenase kinase (PDK-1) (HP vs. AT, 24h, *P=0.007), even the NF-κB and Erk pathways. From the TUNEL assay, the apoptosis in hypoxic preconditioning liver tissue was decreased compared with non-HP operative group at 12h after operation. The expressions of cleaved-caspase 3 (HP vs. AT, *P=0.0119) and PARP (HP vs. AT, *P=0.0134) in HP group were also significantly lower than AT group. CONCLUSION: The hypoxia-induced HIF-1α could promote glucose metabolism to protect hepatocellular mitochondria from damage. It could be a useful way to protect liver against I/R injuries and inflammatory injury, and particularly promote the recovery of graft function.
Asunto(s)
Glucosa/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Precondicionamiento Isquémico , Trasplante de Hígado , Mitocondrias/metabolismo , Daño por Reperfusión/prevención & control , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
BACKGROUND: Overexpression of integrin ß6 plays an important role in a variety of malignant tumor invasion and metastasis. METHODS: The expression levels of integrin ß6, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by immunohistochemistry with human follicular thyroid carcinomas. Then we investigated their correlation with clinical outcomes parameters, relationship, and the survival time. RESULTS: The integrin ß6 staining was expressed in cellular membrane and cytoplasm of follicular thyroid carcinoma cells. The MMP-2 and MMP-9 expressions were mainly found in cellular cytoplasm. In correlation with the clinical outcome parameters of 60 patients, there were significant statistical differences of integrin ß6, MMP-2, and MMP-9 expression levels in different size of tumor. Integrin ß6 and MMP-9 expressions have significant statistical differences in T classifications. MMP-2 and MMP-9 expressions have significant statistical differences in different M classification. Other clinical outcome parameters had no significant statistical differences. CONCLUSION: Integrin ß6 expression correlated significantly with MMP-9 expression, and may be a valuable recurrence indicator for follicular thyroid carcinomas.