Protective effect of miR-146 against kidney injury in diabetic nephropathy rats through mediating the NF-κB signaling pathway.

OBJECTIVE: To study the protective effect of micro ribonucleic acid (miR)-146 against kidney injury in diabetic nephropathy (DN) rats through the nuclear factor-κB (NF-κB) signaling pathway. MATERIALS AND METHODS: In this experiment, 30 adult Sprague-Dawley rats with 5-6 weeks old and weighing 20-30 g were selected and randomly divided into control group (n=10), model group (n=10), and miR-146 Mimic group (n=10, DN rat model + miR-146 Mimic). The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) in the three groups were detected using the full-automatic biochemical analyzer. The protein expression levels of phosphorylated-inhibitor of NF-κB (p-IκB), p-P65, P65, and Tubulin were detected via Western blotting. The messenger RNA (mRNA) of P65 was determined using quantitative Polymerase Chain Reaction (qPCR). Positive expression of p-IκB in tissues was determined using immunohistochemistry. Moreover, the contents of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were detected using the enzyme-linked immunosorbent assay (ELISA) kits. Finally, the apoptosis was detected through Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) dual-fluorescence labeling. RESULTS: The serum levels of Cr and BUN were significantly higher in the model group than those in the control group (p 0.05). The immunohistochemical assay showed that the positive expression of p-IκB in tissues was consistent with those of the protein level as Western blotting revealed. The rats in the model group had evidently increased levels of TNF-α, IL-1β, and IL-6 compared with the control group (p<0.01), while miR-146 Mimic group had evidently decreased levels of them compared with the model group (p<0.01). Finally, apoptosis was enhanced in the model group compared with that in the control group, while it was remarkably inhibited in the miR-146 Mimic group. CONCLUSIONS: MiR-146 can inhibit the NF-κB signaling pathway, lower the levels of TNF-α, IL-1β, and IL-6, and reduce the apoptosis, thereby exerting a protective effect against kidney injury in DN.