Abstract
Purpose To explore the regulatory effects of liraglutide on the kidney and liver through the miR-34a/SIRT1 pathway with related factors in diabetic nephropathy (DN) rats. Methods DN rats were randomly divided into two groups (n = 10) and were injected with liraglutide or normal saline twice a day. The 24-hour urine microalbumin content and biochemical index levels were measured. qRT-PCR was performed to detect the expression of miR-34a in the kidney and liver tissues. The levels of SIRT1, HIF-1a, Egr-1, and TGF-β1 in kidney and liver tissues were determined using qRT-PCR, western blot, and immunohistochemistry. Electron microscopy and HE staining were used to observe the ultrastructure and pathological changes. Results Liraglutide treatment in DN rats decreased blood glucose, 24-hour urine microalbumin, TC, TG, LDL-C, UA, Cr, UREA, ALT, and AST levels and increased the level of HDL-C (P < 0.05). Compared with the control group, the miR-34a levels were significantly decreased in kidney and liver tissues followed by liraglutide treatment (P < 0.05). The levels of SIRT1 in the liraglutide group are significantly higher than those in the control group with the kidney and liver tissues (P < 0.05). Conversely, the contents of HIF-1a, Egr-1, and TGF-β1 were significantly lower in the liraglutide group than in the control group (P < 0.05). Electron microscopy showed that the kidney of the liraglutide-treated group exhibited minor broadening of the mesangial areas, fewer deposits, and a well-organized foot process. HE staining revealed that the kidney of the liraglutide-treated rats had a more regular morphology of the glomerulus and Bowman sac cavity and lighter tubular edema. Additionally, the liraglutide-treated DN rats had a clear hepatic structure, a lower degree of steatosis, and mild inflammatory cell infiltration. Conclusion Liraglutide, through its effect on the miR-34a/SIRT1 pathway, may have a protective role in the kidney and liver of DN rats.
Highlights
Diabetes mellitus (DM) has become a global health problem
The 24-hour urine microalbumin content was significantly reduced in the liraglutide-treated Diabetic nephropathy (DN) rats when compared to the control group (P < 0:05) (Figure 1(b))
Treatment with liraglutide resulted in a significant decrease in the serum levels of total cholesterol (TC), TG, and LDL-C (P < 0:05) (Figures 2(a) and 2(b)); the level of HDL-C was increased (P < 0:05) in DN rats when compared with the control group (Figure 2(b))
Summary
Diabetes mellitus (DM) has become a global health problem. Obesity or overweight, which is caused by lifestyle changes, is an important risk factor for type 2 DM (T2DM) [1, 2]. Diabetic nephropathy (DN) is a common microvascular complication of DM and is an important cause of endstage renal disease. The pathogenesis of DN may be associated with abnormal renal hemodynamics, oxidative stress, and formation of glycosylation end products [3,4,5,6]. The primary pathological changes associated with DN include glomerular sclerosis, renal tubular atrophy, and renal interstitial fibers [7]. In addition to kidney disease, patients with
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