Effect Of Dipeptidyl Peptidase Ⅲ On Myocardium Of Db/db Diabetic Mice

Objective: To study the effect of recombinant dipeptidyl peptidase III on myocardium of diabetic mice in db/db diabetic mice model.Research methods: 16 db/db mice and 8 C57BL/6 mice were divided into 3 groups:PBS control group(PBS group),recombinant dipeptidyl peptidase Ⅲ group(DPP Ⅲgroup)and blank group(Control group),with 8 mice in each group.The PBS and DPP Ⅲgroups were db/db mice,and the Control group was C57BL/6 mice.Mice in DPP Ⅲgroup were injected with 8 μg/g DPP Ⅲ protein through tail vein three times a week,and Control group and PBS group were injected with PBS solution(100 μL/mouse).In the experiment,the body weight of the mice was measured at 0,4 and 8 weeks.Blood samples were collected from the tail of the mice to measure the blood glucose.Blood pressure and heart rate were measured through the tail of the mice.After 8 weeks,the mice in each group were anesthetized and dissected to obtain the blood specimens.Then the hearts were removed after PBS lavage.The contents of total cholesterol and triglycerides in the blood were detected by fully automatic biochemical instrument.Picric sirius acid red staining(PSR staining)was used to observe the myocardium.ELISA was used to detect myocardial interleukin 6(IL-6)and tumor necrosis factor alpha(TNF alpha)content in each group.The relative mRNA expression levels of MCP-1 in myocardial tissue were detected by RT-PCR.Results: 1.Comparison of general items: At the beginning of the experiment,8-week-old db/db mice showed obvious obesity and hyperglycemia compared with the Control group.The body weight and blood glucose level of db/db mice gradually increased.Compared with the PBS group,the parameters above were not affected by DPP Ⅲ treatment(P >0.05).Monitoring of heart rate and systolic blood pressure showed that the hemodynamics in the DPP Ⅲ group or the PBS group did not change during the experiment(P > 0.05).Compared with Control group,the differences in body weight,heart rate,and blood glucose had significant statistics academic significance in the DPPⅢ group and PBS group(P < 0.05).Compared with mice in the Control group,plasma cholesterol or triglyceride levels in the DPP Ⅲ group and PBS group were increased(P<0.01),but DPP Ⅲ treatment did not affect the plasma cholesterol or triglyceride levels(P > 0.05).2.PSR staining showed that the myocardial tissue of the Control group was yellow,the cell size and morphology were normal,and the tissue was normal without fibrosis.In PBS group and DPP Ⅲ group,collagen fibrin tissue around blood vessels which was stained in red color replaced the normal structure of myocardial tissue,and myocardial interstitial collagen proliferated.Compared with the Control group,the degrees of cardiac fibrosis in the DPP Ⅲ group and the PBS group increased,and the degree of fibrosis decreased after DPP Ⅲ treatment.3.Compared with Control group,the expressions of TNF-α and IL-6 in the DPP Ⅲ group and the PBS group were significantly increased(P < 0.05);compared with the PBS group,the expressions of TNF-α and IL-6 in the DPP Ⅲ group were signaly decreased(P < 0.05).4.RT-PCR showed that the expressions of MCP-1 in the PBS group and the DPP Ⅲ group were dramatically increased compared with the Control group(P < 0.01,P < 0.05);compared with the PBS group,the expression of MCP-1 in the DPP Ⅲ group was decreased,and it was statistically significant(P < 0.05).Conclusion: DPP Ⅲ exerts a protective effect on the delay of myocardial fibrosis in db/db diabetic mice by inhibiting the inflammatory response,and its mechanism may be related to MCP-1.