Abstract: Objective To observe the effects of glucagon like peptide-1 (GLP-1) analogues liraglutide on expressions of nitric oxide synthase (NOS) and cyclo-oxygen-ase (COX)2 in renal medulla of type 2 diabetes rats, and the mechanism of its lowering blood pressure and promoting excretion of water and salt in kidney. Methods Type 2 diabetes model rats were generated by high-fat and high-sugar feeding for 8 weeks followed by intraperitoneal injection of streptozotocin (STZ). Subse⁃ quently, eighteen type 2 diabetes rats were divided into two groups: liraglutide treatment group (DMT) and diabetes group (DM). Twelve normal rats were divided into two groups: liraglutide treatment wild type group (WTT) and wild type group (WT). DMT and WTT groups were given liraglutide (200 μg/kg) by subcutaneous injection, DM and WT groups were given equivalent normal saline by the same way. The levels of blood glucose and blood pressure were detected at 0, 2, 4 and 6 weeks after treatment in groups of rats. Samples of urine were collected for detecting ion concentrations (K +, Na+ and Cl-) af⁃ ter treatment for six weeks. Rats were sacrificed and blood samples were collected for detecting ion concentrations (K +, Na+ and Cl-). The expression levels of NOS and COX2 mRNA and protein in renal medulla were detected by real-time PCR and Western blot assay. Results After treating with liraglutide, the values of blood glucose (F=5.933, P < 0.05) and blood pres⁃sure (F=22.070, P < 0.05) were gradually decreased in DMT group. After treatment with liraglutide for 6 weeks, the values of blood glucose (mmol/L:12.78±3.82 vs. 18.75±1.68) and blood pressure (mmHg:119.98±4.43 vs. 136.42±4.48) were signifi⁃ cantly decreased (P < 0.05) in DMT group than those of DM group (P < 0.05). There were no significant differences in the concentrations of K +, Na + and Cl- between the two groups. There were higher levels of K + (mmol/L:46.55±6.43 vs. 33.13± 9.71), Na+ (mmol/L: 56.33±8.83 vs. 41.20±7.25) and Cl- (mmol/L:159.81±25.06 vs. 71.44±12.99) in urine in DMT group than those of DM group (P < 0.05). The mRNA levels and protein expressions of NOS and COX2 in renal medulla were significant⁃ ly increased in DMT group than those of DM group (P < 0.05). Conclusion GLP-1 analogues liraglutide may enhance the expression of COX2 by increasing the expression of NOS to excrete water and salt, and decrease blood pressure.

Key words: glucagon-like peptide-1, liraglutide, renal medulla, type 2 diabetes, nitricoxide synthase, cyclooxygenase 2