RESUMEN
Ischemia-reperfusion (IR) is one of the significant medical problems in China. Triphenyltetrazolium chloride (TTC) staining is used to detect the status of the infarct size, and real-time PCR and western blotting are used to detect expressions of genes. TUNEL assay has been used to detect apoptosis. Using a tree shrew myocardial IR model, we found that in the reperfusion period, resina draconis (RD) treatment reduced the infarct size by TTC staining, and significantly enhanced the superoxide dismutase expression and down-regulated the malondialdehyde concentration in a dose-dependent manner. In hearts showing IR, Bax was increased and Bcl-2 was reduced, and RD treatment inhibited the IR-induced Bax expression and up-regulated the IR suppressed level of Bcl-2. TUNEL assay showed that IR induced the apoptosis of myocardial cells, and RD treatment suppressed the IR-induced apoptosis. CHOP and GRP78 were also upregulated in IR hearts, and RD treatment could significantly attenuate the CHOP and GRP78 levels compared with IR group. We further found that IR decreased the miR-423-3p expression and upregulated its target gene ERK both in mRNA and protein levels, and RD treatment upregulated miR-423-3p expression and downregulated ERK expression compared with the IR group. Importantly, miR-423-3p mimics inhibited IR increased ERK, CHOP and GRP78 expressions, and enhanced IR decreased Bcl-2 expression, and inhibited the IR-induced apoptosis of myocardial cells. The findings of this study suggest that RD treatment inhibited the endoplasmic reticulum induced apoptosis of myocardial cells via regulating miR-423-3p/ERK signaling pathway in a tree shrew myocardial IR model.
Asunto(s)
Cardiotónicos/farmacología , Dracaena/química , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Resinas de Plantas/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Cardiotónicos/aislamiento & purificación , Modelos Animales de Enfermedad , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/genética , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Regulación de la Expresión Génica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Masculino , Malondialdehído/antagonistas & inhibidores , Malondialdehído/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Resinas de Plantas/aislamiento & purificación , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Factor de Transcripción CHOP/genética , Factor de Transcripción CHOP/metabolismo , Tupaiidae , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Proteína Letal Asociada a bcl/genética , Proteína Letal Asociada a bcl/metabolismoRESUMEN
BACKGROUND: Several studies have described heart-type fatty acid-binding protein (H-FABP) from early blood samples as a predictor of outcome in acute pulmonary embolism (PE). This systematic review is designed to determine the prognostic value of H-FABP aimed for use in patients with acute PE. METHODS: Studies published prior to January 2013 in PubMed, Ovid, and Embase were reviewed, and the relationship between H-FABP and the risk of acute PE-related death or serious complications was evaluated. A summary estimate was calculated using the bivariate random-effects approach, and covariate analysis was used to examine sources of heterogeneity among studies. RESULTS: A systematic search revealed six studies containing a total of 618 patients. Elevated H-FABP level was significantly associated with short-term death (within 30 days of embolism) (OR, 40.78; 95% CI, 11.87-140.09) and with complicated clinical events (OR, 32.71; 95% CI, 11.98-89.26). The prevalence of serious complications and death in acute PE was 51% (95% CI, 43%-59%) and 31% (95% CI, 24% -39%), respectively. The combined sensitivity and specificity for the prediction of death and serious complications was 98% and 86%, respectively. CONCLUSIONS: H-FABP is associated with an increased risk of mortality or complicated clinical events in patients with acute PE across different studies with a high degree of clinical and methodologic diversity. The result suggests that H-FABP has significant prognostic value for acute PE.