| Objective:Insulin resistance is one of the most important pathogenesis of type 2 diabetes.It is believed that insulin resistance is a chronic low-grade inflammation.In recent years,resolvin is a new type of anti-inflammatory medium,which is a derivative of ?-3 polyunsaturated fatty acids and inhibits the development of inflammation.Resolvin D1(RVD1)is an important member of ?-3 polyunsaturated fatty acid derivatives.So does RVD1 improve insulin resistance in type 2 diabetic mice? What is the mechanism ? We conducted this study in order to clarify the above problems.Methods:We chose 35 C57BL/6 male mice.High fat diet combined with intraperitoneal injection of small dose of streptozotocin(Streptozotocin,STZ)to establish insulin resistance in type 2 diabetic mice model.Then the mice were randomly divided into blank control group(Con group,n=10),type 2diabetes group(T2DM group,n=10),type 2 diabetes +RVD1 intervention group(T2DM+RVD1 group,n=10).Intraperitoneal injection of RVD1 for 21 days.During the experiment,the body weight and blood glucose were measured periodically.At the end of the experiment,the levels of triglyceride,total cholesterol and insulin were detected.After blood collection,the mice were dissected and fresh liver tissues were taken for the detection of TNF-?,IL-6,p38 MAPK and pp38 MAPK levels.Result:1 Changes in general condition of miceThe general condition of the mice in Con group was good and excretory functions were normal.They have a great mental state,shiny hair,normal diet and no deathmental state.T2 DM group and T2DM+RVD1 group were in poor mental state,dull,slow,polydipsia,polyuria and polyphagia symptoms associated with diabetes.Compared with mice in T2 DM group,the mice in group T2DM+RVD1 were improved.Changes of body weight in mice:During the whole experiment,the weight of mice in Con group increased slowly,T2DM+RVD1 group and T2 DM group gained weight rapidly before modeling and slowly after modeling.Compared with the Con group,the weight of mice in T2DM+RVD1group and T2 DM group were significantly increased in the course of the experiment(P<0.05).There was no significant difference between the T2DM+RVD1 group and the T2 DM group before RVD1 intervention for 1weeks.After the intervention for 2 weeks,the weight of T2DM+RVD1 group was lower than that of T2 DM group(P<0.05).2 Changes of insulin resistance index in mice2.1 Changes of blood glucose in mice:The level of blood glucose in Con group was normal during the whole experiment.T2DM+RVD1 group and T2 DM group showed impaired glucose regulation after 8 weeks of high fat diet and blood glucose was significantly higher fter modeling.Compared with the Con group,the fasting blood glucose of T2 DM group and T2DM+RVD1 group increased significantly,especially after the establishment of type 2 diabetes mellitus(P<0.05).Compared with T2 DM group,T2DM+RVD1 group had no significant change in blood glucose before RVD1 intervention for 1weeks(P>0.05).However,after 2 weeks of RVD1 intervention,the fasting blood glucose of T2DM+RVD1 group was lower than that of T2 DM group(P<0.05).2.2 Changes of blood lipid in mice:Compared with Con group,the total cholesterol and triglyceride of mice in T2 DM group and T2DM+RVD1 group were higher(P<0.05).Compared with T2 DM group,the total cholesterol and triglyceride of mice in T2DM+RVD1 group were lower(P<0.05).2.3 Changes of serum insulin level in mice:Compared with Con group,the insulin levels of mice in T2 DM and T2DM+RVD1 group were significantly higher(P<0.05).Compared with the T2 DM group,the insulin levels of mice in the T2DM+RVD1 group were lower(P<0.05).insulin resistance index of mice in T2 DM and T2DM+RVD1 group were significantly higher(P<0.05).Compared with T2 DM group,the insulin resistance index of mice in T2DM+RVD1 group was significantly lower(P<0.05).2.4 Changes of insulin resistance index in mice:Compared with Con group,the3 Changes of inflammatory markers in liver tissue of mice3.1 Changes of IL-6 and TNF-? expression in the liver in every group:Compared with Con group,the TNF-? and IL-6 levels in liver of mice in T2 DM group and T2DM+RVD1 group were higher(P<0.05).Compared with T2 DM group,the TNF-? and IL-6 in liver of mice in group T2DM+RVD1 were lower(P<0.05).3.2 The Levels of p38 MAPK activation in liver of mice:Compared with Con group,the pp38MAPK/p38 MAPK ratio of liver in T2 DM and T2DM+RVD1group was higher(P<0.05).Compared with the T2 DM group,the pp38MAPK/p38 MAPK ratio of liver in T2DM+RVD1 group was lower(P<0.05).Conclusion:1 RVD1 reduces the levels of weight,blood glucose,triglycerides,total cholesterol,insulin,insulin resistance index and improves insulin resistance in type 2 diabetic mice.2 RVD1 reduces the levels of TNF-? and IL-6 in the liver and improves insulin resistance in the liver.3 RVD1 inhibits the production of inflammatory cytokines in the liver by inhibiting the p38 MAPK inflammatory signaling pathway. |
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