Objective To investigate the expression of miR-122 in renal tissue of diabetes nephropathy mice and the effect of silencing miR-122 on renal tissue of DN mice and its possible mechanism.
Methods The C57BL/6 mouse DN model was established by intraperitoneal injection of streptozotocin (STZ) combined with high sugar and high fat diet. Thirty DN mice were randomly divided into model group, antagomir-NC group and antagomir-122 group with 10 mice in each group. In addition, 10 healthy C57BL/6 mice without any treatment were selected as normal control group. After successful modeling, antagomir-122 group and antagomir-NC group were injected with antagomir-122 and antagomir-NC via tail vein every 7 days respectively for intervention, and the model group and normal control group were injected with the same amount of normal saline via tail vein instead. Eight weeks later, collect the serum and urine, and then kill the mice to obtain kidney samples. The automatic biochemical analyzer detects the quantitative levels of serum creatinine (Cr), urea nitrogen (BUN) and 24-hour urine protein. The periodate Schiff (PAS) staining evaluates the pathological changes of kidney tissue. The qRT-PCR detects the expression level of miR-122 in kidney tissue. The kit detects the levels of glutathione peroxidase (GSH Px), malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney tissue. Western blot detects the Sirt1 α- The expression level of SMA and fibronectin protein.
Results Compared with the normal control group, the glomerulosclerosis score in the model group increased (P<0.05), the miR-122 and α- The expression of SMA and fibronectin protein increased significantly (P<0.05), the level of Cr and BUN in serum, the quantitative level of 24h urinary protein, the level of MDA in renal tissue increased significantly (P<0.05), the level of GSH Px and SOD in renal tissue, and the expression level of Sirt1 protein decreased significantly (P<0.05). there="" was="" no="" significant="" difference="" between="" the="" model="" group="" and="" antagomir="" nc="" p="">0.05). Compared with antagomir NC group, the glomerulosclerosis score in antagomir 122 group decreased (P<0.05) α- The expression of SMA and fibronectin protein decreased significantly (P<0.05), the level of Cr and BUN in serum, the quantitative level of 24h urinary protein, the level of MDA in renal tissue decreased significantly (P<0.05), and the level of GSH Px and SOD in renal tissue, and the expression level of Sirt1 protein increased significantly (P<0.05).
Conclusion The expression of miR-122 in renal tissue of DN mice is elevated. Silencing miR-122 can protect kidney tissue of DN mice through antioxidant stress and fibrosis, and its mechanism may be related to the regulation of Sirt1 gene.