【Animal Modeling】-Effect of DPP4 inhibitor sitagliptin on the expression of Egr-1 and FN in the kidney of ApoE knockout mice

  Objective: To observe the effect of DPP4 inhibitor sitagliptin on the expression of early growth response factor-1 (Egr-1) and fibronectin (FN) in kidney tissue of ApoE knockout mice.

  METHODS: Twelve 8-week-old male ApoE knockout mice were randomly divided into a sitagliptin intervention group (sig+apoE-/- group) and an experimental group (apoE-/- group). 6, and another 6 C57BL mice were taken as the normal control group (control group). After 16 weeks of high-fat diet combined with drug feeding, abdominal cavity tolerance test was performed to observe blood glucose level, and then 24-hour urine samples were collected, and 24-hour urine protein was detected by ELISA. , renal tissue was taken for real-time quantitative PCR and Western blotting to detect the mRNA and protein expression levels of Egr-1 and FN in renal tissue.

  Results: Blood lipid detection showed that the triglyceride, cholesterol, low-density lipoprotein, and very low-density lipoprotein in the experimental group and sitagliptin intervention group were significantly higher than those in the normal control group (P<0.05). there="" was="" no="" significant="" difference="" in="" the="" above="" indicators="" between="" gliptin="" intervention="" groups="" p="">0.05), while the high-density lipoprotein in the sitagliptin intervention group was significantly higher than that in the experimental group (P<0.001) and the normal control group (P<0.001). 3="" ipgtt="" p="">0.05). The 24-hour urine test results showed that the 24-hour urinary albumin excretion in the apoE-/- group was significantly higher than that in the control group, and the difference was statistically significant (P<0.01); after sitagliptin treatment, sig+apoE-/- Compared with the apoE-/- group, the 24-hour urinary albumin of the mice in the group was significantly lower, and the difference was statistically significant (P<0.01). Real-time PCR and Western blotting showed that the mRNA and protein levels of Egr-1 and FN in the renal cortex of the experimental group were higher than those of the normal control group, while sitagliptin could significantly reduce Egr-1 compared with the experimental group. 1 and FN mRNA and protein levels.

  Conclusion: Sitagliptin may down-regulate FN by regulating the expression of Egr-1, thereby achieving renal protection.