| Background: non-alcoholic fatty liver disease(Nonalcoholic fatty liver disease,NAFLD)refers to liver metabolic disease caused by long-term heavy drinking and other definite liver damage factors,which takes the accumulation of lipids in hepatocytes as pathological changes;it can also be used to describe the early benign lesions in the early stage of NASH;and may develop into liver cirrhosis,liver failure,hepatocellular carcinoma,endangering human health.In recent years,the concept of fatty liver disease related to metabolism has been put forward,that is,overweight / obesity,type 2 diabetes and various metabolic disorders are the main causes,in which hepatocyte steatosis is the main pathological feature.and as an initiating factor to participate in the process of fibrosis.Obesity is an independent risk factor for NAFLD.In recent years,with the increasingly prominent problem of overweight and obesity in children and adolescents at home and abroad,the prevalence rate of NAFLD is increasing rapidly.Studies have shown that the liver histopathology of children with NAFLD is different from that of adults,there are different degrees of inflammatory cell infiltration between portal area and / or hepatocytes,accompanied by the proliferation of liver macrophages and the proliferation of surrounding fibrous tissue.NAFLD in children and adolescents is pathologically reversible,so it is very important to clarify the pathogenesis of MAFLD and find effective therapeutic drugs.Gap junction(GJ)is a kind of protein junction channel between adjacent cells,which is composed of gap junction protein(connexins).Its main function is to regulate cell metabolism,internal environment stability,proliferation and division by mediating signal transduction between adjacent cells.Various exogenous and endogenous chemicals can affect the expression of Cx and the level of GJIC in liver.Changes in the structure of liver Cx will lead to changes in GJ permeability and selectivity to permeable substances,which in turn lead to material exchange and information transmission between cells,resulting in abnormal cell function.At present,Cx32,Cx26,Cx37,Cx40,Cx43 has been found in liver tissue.Cxs is a key factor in maintaining the stability of hepatocyte environment,cell division and cell growth and development.Cx43 is expressed in non-parenchymal hepatocytes,such as stellate cells,Kupffer cells and sinusoid epithelial cells.In normal hepatocytes,Cx43 is uniformly distributed in different acinar regions,located in the cell membrane and cytoplasm,mainly in the membrane,which is helpful to the composition of membrane vesicles.Cx43-mediated cell-cell coupling allows signals to spread between hepatocytes,and the expression of Cx43 may be inhibited under normal conditions,but under stress,the expression of Cx43 may be up-regulated,resulting in endoplasmic reticulum dysfunction and insulin resistance.In obesity,Cx43 allows harmful signals to spread between liver cells,leading to fatty liver disease and metabolic changes.Objective: to explore the expression of Cx43 in the liver of mice with liver disease induced by high-fat and high-calorie diet,so as to lay a foundation for further intervention research,and to explore the relationship between the expression of Cx43 and hepatocyte lipid deposition,endoplasmic reticulum stress,inflammatory infiltration and oxidative stress in non-alcoholic liver disease.Methods: 5-week-old C57BL/6J(n = 48)were randomly divided into 2 control groups(D12492).High-fat diet(D12492)was fed respectively to establish NAFLD model,and normal diet(D12450)was used as control(CON).After the establishment of NAFLD model after 13 weeks of feeding,the body weight and net liver weight of mice were measured accurately,and the blood and liver samples of mice were collected.Blood glucose,blood lipid,cholesterol and triglyceride were detected by automatic biochemical analyzer.The degree of liver lesion was observed by HE and oil red O staining.Immunohistochemical staining was used to detect the expression and localization of CX43 in mouse liver tissue,lipid deposition related index CD36,inflammatory infiltration related index CD68,F4bin80(EMR1),and the role of GRP78 and p IRE1 in the relationship with endoplasmic reticulum stress.Conclusion: The expression of CX43 is up-regulated in juvenile mouse NAFLD model.Cx43 participates in and controls the pathological changes of lipid deposition,endoplasmic reticulum stress,inflammatory infiltration and oxidative stress in fatty liver. |
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