Effect of liraglutide on the expression of local renin-angiotensin system and transforming growth factor β1 in the renal tissue of diabetic rats

Abstract

Objective To explore the effects of glucagon-like peptide-1 receptor analog liraglutide(LR) on the expression of local renin-angiotensin system (RAS) and transforming growth factor (TGF)-β1 in renal tissue of diabetic rats. Methods Twenty Wistar rats diabetes models were divided into, diabetic group (DM), and LR-treated group(LR) according to the table of random number after induced by feeding with high-sugary and high-fat diet and injecting of a low dose of streptozotocin into the caudal vein for 8 weeks. And ten healthy Wistar rats were set as normal control(NC). After the establishment of diabetes model, liraglutide (400 μg·kg-1·d-1) was administered by subcutaneous injection for 12 weeks in LR group. And the rats in NC and DM group were injected with saline in the same way. At the end of the trial, the mRNA expression levels of angiotensin Ⅱ(AngⅡ) type 1 receptor (AT1R) and TGF-β1 were detected by real-time quantitative polymerase chain reaction(RT-q PCR), the protein expression levels of AT1R and TGF-β1 were detected by Western blotting(WB) and the protein expression of AngⅡ was detected by enzyme-linked immunosorbent assay(ELISA). Masson staining was used to observe the collagen deposition of renal tissue in rats of different groups. Single factor analysis of variance(ANOVA) was applied in data comparison among the groups, and LSD test were used to analyze the difference between two groups. Results Masson staining showed that DM group had more collagen than NC group in renal tissue, but it was alleviated in LR group. Compared with that in NC group, expressions of AngⅡin renal tissue of DM group was elevated significantly(t=3.444, P<0.05), and it was down-regulated significantly in LR group thant that in DM group(t=2.614, P<0.05). The mRNA and protein expression of AT1R and TGF-β1 in renal tissue in DM group were significantly higher than those in NC group(t=4.084, 3.714, 9.381, 6.408, all P<0.05), and all were down-regulated significantly in LR group when compared with those in DM group(t=3.487, 2.907, 5.033, 2.295, all P<0.05). Conclusion Liraglutide plays a role of organ-protecting by inhibiting the expression of TGF-β1 in renal tissue of diabetic rats, and this may be related with the down-regulating of local RAS. Key words: Diabetes mellitus; Liraglutide; Renin-angiotensin system; Transforming growth factor beta 1; Rats