Objective To investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1
(Egr-1) and fibronectin in the kidney of ApoE gene knockout mice. Methods Eight-week-old male ApoE gene knockout mice
were randomly divided into sitagliptin + apoE-/- group and apoE-/- group (n=6), with 6 C57BL mice as the normal control group.
After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test
(IPGTT) and were measured for 24-h urinary albumin using ELISA. All the mice were then sacrificed to examine the changes
of blood lipid profile and for detection of Egr-1 and fibronectin mRNA and proteins in the renal tissue using real-time PCR and
Western blotting. Results The mice in both apoE-/- group and sitagliptin+apoE-/- group all showed prominently increased blood
lipids as compared with the control group (P<0.05) without significant differences between the two apoE-/- groups. The level of
HDL was significantly higher in sitagliptin +apoE-/- group than in apoE-/- group (P<0.001) and control group (P<0.001). IPGTT
showed no significant differences in the levels of blood glucose among the 3 groups. The excretion of urinary albumin was
increased in apoE-/- group compared with the control group (P<0.01), but was significantly lower in sitagliptin+ apoE-/- group
than in apoE-/- group (P<0.01). Real-time PCR and Western blotting showed significantly decreased mRNA and protein
expressions of renal cortical Egr-1 and fibronectin in sitagliptin + apoE-/- group compared with apoE-/- group. Conclusion
Sitagliptin can reduce the renal expression of fibronectin by regulating the expression of Egr-1 to achieve renal protection.
