Exploring The Model Of Caerulein Induced Pancreatitis In Mice And Adipokines Predicts Persistent Organ Failure In Preliminary Clinical Study

BackgroundMany models can be used to study acute pancreatitis. Because its easy-to-inducing, non-invasive, reproducible, and close to the human characteristics of acute pancreatitis, caerulein intraperitoneal injection has been widely applied. We often need to study the pancreatitis in different severity, but there is not a model of acute pancreatitis was progressive change, so it is necessary to explore the model of pancreatitis of caerulein induced in-depth, and this study is to observe the change of severity of acute pancreatitis induced by intraperitoneal injection of caerulein at different doses in mice.Apart from common inflammatory substances, such as IL-6, IL-8, IL-10, CRP, etc, involved in the development of pancreatitis of different severity. In recent years, adipokines as a regulator of the inflammatory response is closely associated with the onset of pancreatitis. But now there is not a clinical studies about a variety of adipokines and the severity of pancreatitis. This study intends to explore the relationship between changes in adipokines and severity of pancreatitis, and these changes are compared with APACHE-II score. This study focused on researching the sensitivity and specificity of adipokines in predicting persistent organ failure, and laying the foundation for clinical application. Study one Exploring and improving mouse model of pancreatitis AimTo establish mild and severe acute pancreatitis induced by the same cause. MethodsThere are two ways to establish the model of acute pancreatitis. Acute pancreatitis(AP) was induced by intraperitoneal infection of 50 ug/kg caerulein at 3 times, 6 times, 9 times, 12 times, respectively. The other model of pancreatitis was induced by 12 hourly intraperitoneal infections of different concentrations caerulein at 10ug/kg, 50ug/kg, 250ug/kg, respectively. We evaluated the severity of AP biochemically and morphologically. ResultsConventional doses of caerulein(50 ug/kg) were injected with 3, 6, 9, 12 times, the level of serum amylase in experimental group were significantly higher than that in control group(P<0.05), peaked in the 9 times(25966.67±3787.02 U/L); pancreatic water content in the experimental group was significantly higher than that in control group(P<0.05), peaked in the 6 times(81.13±1.03%); pancreatic tissue HE staining showed that pancreas was slightly edema and infiltration of inflammatory cells at 3 times, which showed a large amount of neutrophil infiltration and obvious edema at the 6 times, and pancreatic leaflet margin appeared a small amount necrosis at the 9 times, and the acinar necrosis foci could be seen in large range at the 12 times(histopathological score 8.20±0.84), the microscope exhibited altered necrotizing pancreatitis. In the group of different concentrations caerulein, the serum amylase, lipase and pancreatic water content in the experimental group were significantly higher than that in control group(P<0.05), peaked in the group of 50ug/kg. Pancreatic tissue HE staining showed that pancreas was localized infiltration of inflammatory cells and mild edema in the group of 10ug/kg; the feature of 50ug/kg group has been aforementioned; the feature of 250ug/kg group showed that there was a large sheet of pancreatic acinar necrosis and local missing part of leaflet structure under the microscope. ConclusionsWith increasing dose of caerulein, the severity of pancreatitis was gradually increased in a certain range. Conventional caerulein doses(50 ug/kg) may induce acute edematous pancreatitis by 6 times of intraperitoneal injection in mice,and 12 times may induce acute necrotizing pancreatitis. Study two Adipokines Predicts Persistent Organ Failure in Preliminary Clinical Study AimTo study the serum level of adipokines in the patients with different severity of pancreatitis; to investigate the accuracy of resistin, leptin and adiponectin in predicting persistent organ failure in AP. MethodsThe data of 90 consecutive patients admitted to our hospital for AP were retrospectively collected from an ongoing prospective cohort study. The levels of adiponectin, leptin and resistin were measured and were compared between patients with and without persistent organ failure. The accuracy of the adipokines in predicting persistent organ failure were compared with the APACHE-II score, and were separately investigated in the overweight and the non-overweight groups. ResultsThe levels of resistin significantly increased in AP patients with persistent organ failure, both in the overweight and the non-overweight subgroups. Resistin and APACHE-II score predicted persistent organ failure with comparable AUCs of 0.72 and 0.75(p=0.66). Resistin demonstrated similar accuracy with APACHE-II score in predicting persistent organ failure in the subgroup of overweight(0.69 vs. 0.66, p=0.82) and non-overweight(0.76 vs. 0.87, p=0.39). No correlation between adiponectin and persistent organ failure, and a weak correlation between leptin and persistent organ failure was demonstrated. ConclusionsSerum resistin levels were significantly elevated in AP patients with persistent organ failure. Resistin and leptin correlate with the persistent organ failure in AP, and this factor may be used to predict the persistent organ failure in AP.