Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway

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 ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>n</a:mi> <a:mo>=</a:mo> <a:mn>10</a:mn> </a:math> ) 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 ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> <c:mo><</c:mo> <c:mn>0.05</c:mn> </c:math> ). Compared with the control group, the miR-34a levels were significantly decreased in kidney and liver tissues followed by liraglutide treatment ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo><</e:mo> <e:mn>0.05</e:mn> </e:math> ). The levels of SIRT1 in the liraglutide group are significantly higher than those in the control group with the kidney and liver tissues ( <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo><</g:mo> <g:mn>0.05</g:mn> </g:math> ). Conversely, the contents of HIF-1a, Egr-1, and TGF-β1 were significantly lower in the liraglutide group than in the control group ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>P</i:mi> <i:mo><</i:mo> <i:mn>0.05</i:mn> </i:math> ). 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.