The Role And Mechanism Of GSK-3? Inhibitor TDZD-8 In Hyperlipidemic Acute Pancreatitis In Mice

Objective:To investigate the protective effect and mechanism of GSK-3?inhibitor TDZD-8 on hyperphagic pancreatitis induced by cerulein and P407.Methods:Nine male mice were randomly divided into Control group,Hyperlipidemia pancreatitis group?HAP group?and Treatment group,n=3.Water was banned from the experiment 12h before the experiment.The HAP group and Treatment group were injected with P407?0.5g/Kg?from the experiment 24h before the experiment.HAP group mice were injected intraperitoneally with caerulein?50?g/Kg?and injected once per hour for 7 times.Treatment group received the same injection of caerulein from HAP group,but after the seventh injection of caerulein,the TDZD-8 was injected intraperitoneally once?10 mg/Kg?.In HAP group,the same amount of physiological saline was intraperitoneally injected at the same time as the control group.Each group of mice was induced for 5h,then anesthesia with sodium pentobarbital.Pancreatic specimens were collected.Part of the pancreas was HE stained to observe the pathological changes of the pancreas.RT-PCR was used to detect pancreatic tissue TNF-?,IL-1?.And IL6 mRNA expression,Western-blot detection of pancreatic tissue NF-?Bp65,phospho-p65 and?-catenin expression.The RT-PCR data were analyzed with 2^-??Ct.The remaining data were quantitative data,expressed as mean±standard deviation.Statistical analysis was performed using statistical software SPSS19.0.The student't test was used to compare the two groups.P<0.05 indicates that the difference has Statistical significance in these group.Results:1.Under light microscope,the pancreas injury was obvious in the HAP group,and the percentage of inflammation and pancreatic necrosis area was statistically significant compared with the control group?P<0.05?.In Treatment group,the pancreatic injury was reduced.Compared with HAP group,the percentage of inflammation and pancreatic necrosis decreased significantly?P<0.05?.2.The expression of TNF-?,IL-1?and IL-6 mRNA in pancreatic tissue of HAP group was significantly higher than that in Control group?P<0.05?.However,the expression levels of TNF-?,IL-1?and IL-6 mRNA in the pancreatic tissue of Ttreatment group and HAP group were decreased,and the difference was statistically significant?P<0.05?.3.The ratio of phosphorylated p65/p65 in pancreatic tissue of HAP group was significantly higher than that of Control group,but decreased in Treatment group compared with HAP group?P<0.05?.In HAP group,?-catenin was increased in the pancreas compared with Control group,while?-catenin in the pancreas of the treated group was also significantly higher than that in HAP group,and the difference was statistically significant?P<0.05?.Conclusion:1.The HAP model of mice was successfully induced by intraperitoneal injection of cerulein and P407.2.GSK-3?inhibitor TDZD-8 can reduce the damage of mouse pancreatic tissue induced by caerulein and P407,and the mechanism of inflammation may be related to the activation of Wnt pathway and the inhibition of transcriptional activity of NF-?B pathway.