| Objective: Non-alcoholic fatty liver disease(NAFLD)is a common liver disease with a high incidence worldwide.Most of its patients are obese.Although weight loss can control the disease to a certain extent and even reverse liver disease,The implementation and persistence of weight loss treatment are often unsatisfactory,and the treatment effect is difficult to achieve expectations.Therefore,more and more patients progress from simple non-alcoholic fatty liver(NAFL)to non-alcoholic steatohepatitis(NASH).After entering this stage,the risk of further progression of the disease to liver fibrosis,cirrhosis and even hepatocellular carcinoma is significantly increased.Therefore,it is of great significance to find a therapeutic method that can inhibit the further development of non-alcoholic fatty liver and non-alcoholic steatohepatitis.So far,many studies on the occurrence and development mechanism of nonalcoholic fatty liver disease have made people have a more in-depth understanding of the disease.However,there is currently no effective drug to inhibit the progression of non-alcoholic fatty liver disease in clinical practice.Pantoprazole(PPZ)is a kind of proton pump inhibitor,and its main clinical application is the treatment of related diseases caused by abnormal secretion of gastric acid.In addition to these applications,more and more new studies in recent years have revealed the role of proton pump inhibitors in stabilizing and protecting cell membranes,inhibiting the production of inflammatory cytokines,anti-oxidation,and inhibiting fibrosis.Therefore,the purpose of this project is to study the effect of pantoprazole on the expression levels of inflammatory cytokines in the liver tissue of the mouse HFHC diet model,in order to find an effective drug to inhibit the progression of nonalcoholic fatty liver disease,prevent or even reverse Liver disease,improve the prognosis of patients with chronic nonalcoholic fatty liver disease,and provide more theoretical basis for the prevention and treatment of non-alcoholic liver disease.Methods:1.Pretreatment of C57BL/6J male mice aged 4-6 weeks: After one week of free water and normal chow feeding,8 mice that continued to eat normally were selected as the control group,and the remaining mice were fed high Fat High Cholesterol(HFHC)Diet:High fat(42%)plus high cholesterol(0.2%).After 4 weeks of HFHC diet feeding,mice were randomly divided into 3 groups: model group(HFHC),pantoprazole 2 mg/kg group(HFHC + PPZ 2mg/kg),pantoprazole 5 mg/kg group(HFHC+PPZ 5mg/kg);then the corresponding treatment for each group was started,and HFHC diet feeding was continued during the treatment period,including 7 of HFHC group,6 of HFHC+PPZ 2mg/kg group and 7 of HFHC+PPZ 5mg/kg group.Mice were treated with PPZ or sterile water for 16 weeks.n>5 in each group.2.After the above treatment is completed,the total body weight of each mouse is first weighed,then the mice are sacrificed,the mouse liver is taken out and weighed,the total body weight and liver weight are recorded respectively,and the liver index is calculated and compared.3.The liver of each mouse was cut out,and HE staining was used to observe whether the model was established successfully and the effect of pantoprazole on the steatosis and inflammatory lesions of the mouse liver.4.After the treatment,the sent gene chip inspection indicated that the expression of the following indicators in the mouse liver tissue was up-regulated: CXCL1,CXCL5,CCL2,CCR2,CD14,CD74,IL-6,IL-1α,IL-1β,TNF-α;these indicators were further verified by q RT-PCR and compared between groups..Results:1.The statistical results of total body weight showed that the total body weight of the HFHC group was significantly higher than that of the normal group,and the difference was statistically significant(P<0.05,P<0.01).The total body weight of the HFHC+PPZ2mg/kg group was lower than that of the HFHC group.,the difference was statistically significant(P<0.05),the overall body weight of the HFHC+PPZ 5mg/kg group was lower than that of the HFHC group,and the difference was statistically significant(P<0.05).2.The statistics of liver weight showed that the liver weight of the HFHC group was significantly higher than that of the normal group,and the difference was statistically significant(P<0.05,P<0.01).The liver weight of the HFHC+PPZ 2 mg/kg group was lower than that of the HFHC group.,the difference was statistically significant(P<0.05).The liver weight in the HFHC+PPZ 5mg/kg group was lower than that in the HFHC group,and the difference was statistically significant(P<0.05).3.The statistical results of liver index showed that the liver index of the HFHC group was higher than that of the normal group,and the difference was statistically significant(P<0.05,P<0.01).The liver index of the HFHC+PPZ 2mg/kg group was lower than that of the HFHC group.The difference was statistically significant(P<0.05).4.The results of HE staining showed that in normal mouse liver tissue,hepatocytes,hepatic sinusoids and hepatic cords were normal in morphology and complete in structure.No lipid droplets or ballooning changes;compared with the normal group,the HFHC group had increased hepatocyte volume,disordered arrangement of nuclei,obvious ballooning changes,a large number of lipid droplets and inflammatory cell infiltration.In HFHC+PPZ 2 mg Ballooning,lipid droplets,and inflammatory cell infiltration were reduced in the /kg group,and these improvements were more pronounced in the HFHC+PPZ 5 mg/kg group.5.The results of q RT-PCR experiments showed that among the detected indicators,the expression level of CCL2 m RNA in the HFHC group was significantly higher than that in the normal group,and the difference was statistically significant(P<0.05,P<0.01),and the HFHC+PPZ The expression level of CCL2 m RNA in the 2 mg/kg group was lower than that in the HFHC group,and the difference was statistically significant(P<0.05).The expression level of IL-1α m RNA in the HFHC group was significantly higher than that in the normal group,and the difference was statistically significant(P<0.05,P<0.01).Compared with the HFHC group,the difference was statistically significant(P<0.05).Conclusion:1.Pantoprazole inhibits the progression of obesity in mice in a high-fat,high-cholesterol(HFHC)diet model.2.In a high-fat and high-cholesterol(HFHC)diet model in mice,pantoprazole can inhibit the progression of liver steatosis and inflammation in mice.3.Pantoprazole can reduce the expression levels of CCL2 and IL-1α in mouse liver tissue in a mouse high-fat and high-cholesterol(HFHC)diet model.4.Pantoprazole is a potential drug for the clinical treatment of nonalcoholic fatty liver disease. |
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