Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP.

Golden Syrian hamsters are small rodents, but they display many features that resemble the physiology and metabolism of humans. [7], all of which are not observed in other rodents such as mice and rats. Consequently, hamsters, like humans, exhibit enhanced susceptibility to atherosclerosis (AS) and diabetes [8], which led to the widespread use of hamsters in studies on AS and diabetes.In the past 2-3 decades, due to the fast development of transgenic and knockout mice, hamsters were gradually replaced by these mouse models. However, due to multiple differences between mice and humans with respect to physiology and metabolism, the use of genemanipulated mice has limited value in disease modeling and pathophysiological studies. Extensive literature search has revealed an absence of reports on genetically manipulated hamster models. To capitalize on the special metabolic features of hamsters, we aim to generate genemanipulated hamsters as an alternate rodent model for general applications. As the initial step to create a genetically manipulated hamster, we utilized a highly efficient lentiviral vector to generate transgenic hamsters expressing enhanced green fluorescent protein (eGFP).By modifying and optimizing the protocols for producing transgenic mice and rabbits in our laboratory [9, 10], we developed a specific procedure for hamster superovulation, fertilized egg harvesting, perivitelline space microinjection and embryo transfer. After the successful culture of fertilized hamster eggs that developed into 4-and 8-cell embryos in vitro ( Figure 1A), we implanted these embryos into pseudopregnant females. We obtained 7-10 pups/litter in 4 out of 7 surrogate mothers. Next, we microinjected 50-100 picoliters of a lentiviral

No abstract

Hypertriglyceridemic pancreatitis (HTGP) is often encountered clinically as a common form of recurrent acute pancreatitis (AP). It is important to evaluate the management of severe hypertriglyceridemia (HTG) or anti-inflammation in the prophylaxis of HTGP in the clinic. FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1, 3-propanediol) is a new anti-inflammatory agent with low toxicity and reported to ameliorate lung injury with pancreatitis in rat. We evaluated its protective affection on AP induced by seven hourly intraperitoneal injection of cerulein in apolipoprotein CIII transgenic mice with severe HTG. FTY720 at 1.5 mg/kg was administered by gastric lavage daily for 3 days before induction of AP. The effects of FTY720 to protect against HTGP were assessed by serum amylase, pancreatic pathological scores, immunostaining, and the expression of inflammatory cytokine genes. As a result, injection of cerulein resulted in more severe pathological changes of AP and higher monocyte chemoattractant protein 1 expression in the pancreas in transgenic than in nontransgenic mice. FTY720 pretreatment improved the pathological severity of AP and decreased the expression of monocyte chemoattractant protein 1 in the pancreas significantly, especially near fourfold reduction in transgenic mice. However, FTY720 did not affect plasma triglyceride levels, and other inflammatory factors and plasma amylase were not correlated with the extent of pancreatic damage in AP with or without FTY720 administration. In summary, our study in a new model, apolipoprotein CIII transgenic mice, demonstrated that HTG mice are susceptible to induction of AP. Prophylactic treatment of FTY720 can significantly attenuate cerulein-induced AP and hence warrant further investigation of sphingosine-1-phosphate receptors agonist for potential clinical application in recurrent attacks of HTGP.