RESUMEN
Sick sinus syndrome (SSS), a complex type of cardiac arrhythmia, is a major health threat to humans. Shenfu injection (SFI), a formula of traditional Chinese medicine (TCM), is effective in improving bradyarrhythmia. However, the underlying mechanism of SFI's therapeutic effect is subject to few systematic investigations. The purpose of the present research is to examine whether SFI can boost the differentiation effectiveness of bone marrow mesenchymal stem cells (BMSCs) into pacemaker-like cells and whether the transplantation of these cells can improve the pacing function of the sinoatrial node (SAN) in a rabbit model of SSS. BMSCs from New Zealand rabbits were extracted, followed by incubation in vitro. The flow cytometry was utilized to identify the expression of CD29, CD44, CD90, and CD105 surface markers. The isolated BMSCs were treated with SFI, and the whole-cell patch-clamp method was performed to detect hyperpolarization-the activated cyclic nucleotide-gated potassium channel 4 (HCN4) channel current activation curve. The SSS rabbit model was established using the formaldehyde wet dressing method, and BMSCs treated with SFI were transplanted into the SAN of the SSS rabbit model. We detected changes in the body-surface electrocardiogram and recorded dynamic heart rate measurements. Furthermore, transplanted SFI-treated BMSCs were subjected to HE staining, TUNEL staining, qPCR, western blotting, immunofluorescence, immunohistochemistry, and enzyme-linked immunosorbent assay to study their characteristics. Our results indicate that the transplantation of SFI-treated BMSCs into the SAN of SSS rabbits improved the pacing function of the SAN. In vitro data showed that SFI induced the proliferation of BMSCs, promoted their differentiation capacity into pacemaker-like cells, and increased the HCN4 expression in BMSCs. In vivo, the transplantation of SFI treated-BMSCs preserved the function of SAN in SSS rabbits, improved the expression of the HCN4 gene and gap junction proteins (Cx43 and Cx45), and significantly upregulated the expression of cAMP in the SAN, compared to the SSS model group. In summary, the present research demonstrated that SFI might enhance the differentiation capacity of BMSCs into pacemaker-like cells, hence offering a novel approach for the development of biological pacemakers. Additionally, we confirmed the effectiveness and safety of pacemaker-like cells differentiated from BMSCs in improving the pacing function of the SAN.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Células Madre Mesenquimatosas/efectos de los fármacos , Síndrome del Seno Enfermo/tratamiento farmacológico , Nodo Sinoatrial/efectos de los fármacos , Animales , Diferenciación Celular , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Masculino , Conejos , TransfecciónRESUMEN
The impacts of ethanol pretreatment and blanching on moisture transfer, microstructure, and nanostructure of cell-wall polysaccharides of apple slices were studied. The physicochemical properties, namely, color, rehydration, and antioxidant capacity were also evaluated. The results corroborated that the use of ethanol and blanching reduced drying time 45-60% and 21-42% at various drying temperatures (50, 60, 70, and 80 °C), respectively, compared to controls. Ethanol loosened the cell wall structure, thereby reducing the internal resistance of moisture diffusion, and the changes in cell wall structure caused by blanching were mainly due to the ß-elimination degradation of pectins. Both samples of ethanol pretreatment and blanching possessed lower browning index and higher antioxidant capacity compared with the untreated ones. Overall, ethanol pretreated products exhibited the shortest drying time, less color change and higher antioxidant capacity. These results provide new insights on possible mechanisms about ethanol pretreatment and blanching to improve drying.