Liraglutide promotes the reduction of blood pressure and drives the water and salt through in renal medulla of type 2 diabetes rats
10.11958/20150245
- VernacularTitle:利拉鲁肽对2型糖尿病大鼠降血压、利水盐的作用机制探讨
- Author:
Shaoqing WANG
;
Nan MAO
;
Ping ZHOU
;
Li WANG
;
Fang GAO
;
Yixun WEI
;
Junming FAN
;
Ping FU
- Publication Type:Journal Article
- Keywords:
glucagon-like peptide-1;
liraglutide;
renal medulla;
diabetes mellitus,type 2;
nitric oxide synthase;
cyclo-oxygenase 2
- From:
Tianjin Medical Journal
2016;44(7):849-852,853
- CountryChina
- Language:Chinese
-
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 (200μg/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.