RESUMEN
BTB and CNC homology 1 (BACH1) regulates biological processes, including energy metabolism and oxidative stress. Insufficient liver regeneration after hepatectomy remains an issue for surgeons. The Pringle maneuver is widely used during hepatectomy and induces ischemia/reperfusion (I/R) injury in hepatocytes. A rat model of two-thirds partial hepatectomy with repeated I/R treatment was used to simulate clinical hepatectomy with Pringle maneuver. Delayed recovery of liver function after hepatectomy with the repeated Pringle maneuver in clinic and impaired liver regeneration in rat model were observed. Highly elevated lactate levels, along with reduced mitochondrial complex III and IV activities in liver tissues, indicated that the glycolytic phenotype was promoted after hepatectomy with repeated I/R. mRNA expression profile analysis of glycolysis-related genes in clinical samples and further verification experiments in rat models showed that high BACH1 expression levels correlated with the glycolytic phenotype after hepatectomy with repeated I/R. BACH1 overexpression restricted the proliferative potential of hepatocytes stimulated with HGF. High PDK1 expression and high lactate levels, together with low mitochondrial complex III and IV activities and reduced ATP concentrations, were detected in BACH1-overexpressing hepatocytes with HGF stimulation. Moreover, HO-1 expression was downregulated, and oxidative stress was exacerbated in the BACH1-overexpressing hepatocytes with HGF stimulation. Cell experiments involving repeated hypoxia/reoxygenation revealed that reactive oxygen species accumulation triggered the TGF-ß1/BACH1 axis in hepatocytes. Finally, inhibiting BACH1 with the inhibitor hemin effectively restored the liver regenerative ability after hepatectomy with repeated I/R. These results provide a potential therapeutic strategy for impaired liver regeneration after repeated I/R injury.
Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Metabolismo Energético , Hepatectomía , Hepatocitos , Regeneración Hepática , Estrés Oxidativo , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Humanos , Masculino , Ratas , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Metabolismo Energético/fisiología , Hepatocitos/metabolismo , Regeneración Hepática/fisiología , Estrés Oxidativo/fisiología , Daño por Reperfusión/metabolismoRESUMEN
OBJECTIVE: Malignant biliary obstruction (MBO) is a rare disease with a poor prognosis. Recent studies have shown that endoscopic radiofrequency ablation (ERFA) may improve survival. We conducted a systematic review and meta-analysis of the efficacy of ERFA in combination with biliary stent placement for the treatment of MBO. METHODS: The study was registered in INPLASY (number 202340096). The PubMed, Cochrane Library, Web of Science, and Embase databases were searched from inception to April 2023. We selected studies comparing the efficacy of ERFA plus stent placement with stent placement alone. The primary outcomes were pooled hazard ratios (HRs) for overall survival and stent patency; the secondary outcomes were the odds ratios (ORs) for adverse events. RESULTS: Eleven studies (four randomized controlled trials and seven observational studies) were included in the meta-analysis. Pooled analysis showed a difference in survival time between the two groups (HR 0.65, 95% confidence interval [CI] 0.58-0.73, I2 = 40%). However, there were no differences in the duration of stent patency or the incidence of adverse events (HR 1.04, 95% CI 0.84-1.29, I2 = 46%; OR 1.41, 95% CI 1.02-1.96, I2 = 29%). CONCLUSIONS: ERFA has a significant survival benefit for MBO, but does not increase the risk of adverse events.