RESUMEN
Background: Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway. Methods: The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats' pancreatic histopathology and mortality were assessed. Results: Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage. Conclusion: The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.
RESUMEN
Oil pollution influences marine biology, ecology, and regional sustainable development capacity, but model uncertainties limit the ability of the numerical model to accurately predict the transport and fate of the underwater oil spill. Based on a three-dimensional underwater oil spill model validated by satellite images of the oil slick at the sea surface, the Penglai 19-3 oil spill accident in the Bohai Sea was simulated; in addition, several sensitivity experiments were set up to investigate the influence of model uncertainties in the background wind, current, start time of the oil spill, and spill site on the transport of underwater spilled oil in the Penglai 19-3 oil spill accident. The experimental results indicate that the uncertainty in the background wind has a certain impact on the simulated centroid position at the sea surface, and little effect on the simulated underwater results, while the uncertainty in the background current has a significant influence on the transport of the underwater spilled oil both at the sea surface and underwater. An uncertainty of 24 h in the start time of the oil spill can cause more than 1 time larger than the benchmark case displacement of the oil spill centroid point and sweeping area at the sea surface, as the periodic tidal current is the main constituent of the ocean current in the Bohai Sea. The uncertainty in the spill site has a large influence on the final position of the oil spill centroid point, but the oil spill trajectories do not intersect with each other within 48 h, which makes it possible to identify the oil spill platform from the actual observations. The influence of uncertainties in the important model inputs and key model parameters on the transport of underwater spilled oil in the Penglai 19-3 oil spill accident is evaluated for the first time, which is of substantial significance for improving the prediction accuracy of the transport and fate of underwater oil spills.