The Protective Effects Of Caffeine On Severe Acute Pancreatitis And Its Mechanisms In Obesity Mice

ObjectiveTo explore the protective effects of caffeine on severe acute pancreatitis and its mechanisms in obesity mice.MethodsThis experiment was designed to investigate the effects of caffeine on obese-associated severe acute pancreatitis.Mice were fed with normal diet(ND)or high fat diet(HFD)four weeks,then additing 0.05% caffeine with their water in following four weeks.And experimental AP was induced in mice via seven hourly injections of cerulein(50 ?g/kg).Severity of AP was assessed by biochemical markers and histology scores of pancreas,liver,lung.Serum cytokines levels are determined for assessing the extent of system inflammatory response.The endoplasmic reticulum stress–associated protein and NF-?B were assesed by Western Blot and Immunohistochemical.ResultsOur results demonstrate that AP is more severity in HFD compared with ND.However,caffeine administration in obese mice induced AP significantly reduced serum lipase and amylase(P<0.05),the levels of serum TNF-?,IL-6 and MCP-1(P<0.05),and liver injury,as well as lung injury compared to AP in obese mice without caffeine.These results suggested that caffeine is capable of alleviating pancreas pathology damage and other tissues injury in obese mice with AP.What?s more,the caffeine also decreased the expression of endoplasmic reticulum stress–associated protein(GRP78?IRE1a?CHOP)and NF-?B in obesity mice with AP.ConclusionTaken together,these data indicate that caffeine may constitute a prevention strategy in the obese-associated severe acute pancreatitis.Caffeine not only alleviating the severity of SAP and other organs injury in obesity mice through improving the disruption of lipid metabolism,but also decreasing the expression endoplasmic reticulum stress–associated protein and NF-?B in obesity mice with AP.