The Effect And Mechanism Of Monocyte Chemotactic Protein 1-induced Protein 1(MCPIP1) In Acute Alcoholic Pancreatic Injury

Background Acute pancreatitis(AP)is a common clinical acute abdomen,which mainly manifests as acinar injury,oxidative stress and pancreatic inflammation.In patients with acute pancreatitis,severe pancreatitis(Severe acute pancreatitis,SAP)patients can account for15%-30%,which can lead to multiple organ failure,and the mortality rate is as high as40%.Excessive release of inflammatory mediators is one of the important causes of acute pancreatic injury.Monocyte chemoattractant protein-1 induced protein 1(MCPIP1)is an important regulator of inflammatory response and immune homeostasis.Previous experiments have found that acute alcohol exposure can cause pancreatic damage in mice.Accompanied by increased expression of monocyte chemoattractant protein-1((monocyte chemoattractant protein 1,MCP-1)and its receptor CC chemokine receptor-2(CC chemokine receptor 2,CCR2)and MCPIP1,and activation of the pathway gene GSK3β,JNK and pc-Jun.But so far,the role of MCPIP1 in acute alcoholic pancreatic injury is still unclear.ObjectiveAn animal model of MCPIP1 silencing was constructed by disrupting ZC3H12 A gene with a short hairpin RNA(sh RNA).After acute alcohol exposure,the expressions of inflammation-related factors and related pathway indicators in mice models with MCPIP1 silence were observed to explore the regulatory role and related mechanisms of MCPIP1 in acute alcoholic pancreatic injury.Methods:ShRNA sequence was designed according to mouse ZC3H12 A gene sequence.MPC-83 cells were infected with lentivirus-mediated sh RNA,and the sh RNA sequences with the highest inefficiency were selected by q PCR and Western blot.Mice were given alcohol gavage after retrograde pancreatic duct injection of lentivirus,and an animal model of acute alcohol exposure-induced pancreatic injury induced by MCPIP1 knockdown was established.H&E staining,q PCR,Western blot,ELISA and other methods were used to detect the levels of proinflammatory factors,chemokines and MAPK pathways indicators.Results:1.MCPIP1 knockdown aggravated the damage of alcohol exposure to the structure of mouse pancreas.2.MCPIP1 knockdown up-regulated the levels of α-amylase and lipase in the serum of mice after acute alcohol exposure.3.MCPIP1 knockdown increased the m RNA and protein expression levels of proinflammatory factors IL-6,IL-1β,chemokine MCP-1 and its receptor CCR2 in mouse pancreatic tissue after acute alcohol exposure.4.MCPIP1 knockdown significantly increased the phosphorylation levels of JNK and Erk induced by acute alcohol exposure.Conclusion:1.MCPIP1 can inhibit the expression of inflammatory factors and play a negative regulatory role in acute alcoholic pancreatic injury.2.MCPIP1 may exert its activity by inhibiting the phosphorylation of ERK and JNK in the MAPK signaling pathway.