To explore the protective effects of orphan nuclear receptor subfamily 2 group E member 1 (NR2E1) overexpression on nerve regeneration in dentate gyrus (DG) of diabetic rats complicated with depression.

The rat model of diabetes complicated with depression was established by injecting streptozotocin into the tail vein combined with chronic unpredictable mild stimulation. The successful rats were randomly divided into model, control and experimental groups, with 8 rats per group; another 8 normal rats were set as normal group. Control group was injected adeno-associated control virus 4 μL. Experimental group was injected with adeno-associated virus of overexpress NR2E1 4 μL; model and normal groups were injected with 0.9% NaCl. After 14 days, the depression-like behavior of rats was detected by Morris water maze, the fasting blood glucose level was detected by blood glucose meter, and the serum insulin (INS), interleukin -1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in DG area were detected by enzyme-linked immunosorbent assay. The expression of thymidine analogue bromodeoxyuridine (Brdu) in DG region was detected by immunofluorescence method, and the signal transduction expression levels of microRNA-let-7d (miRNA-let-7d)/NR2E1/silencing information regulatory factor 1 (SIRT1) gene were detected by real-time fluorescence quantitative polymerase chain reaction.

The space exploration time of experimental, control, model and normal groups was (31.25±9.94), (25.50±8.02), (19.75±5.82) and (43.87±12.77) s; the fasting blood glucose were (19.28±3.60), (25.26±5.25), (23.71±4.13) and (4.45±0.40) mmoL·L^-1; the insulin levels were (77.15±3.03), (80.53±4.93), (83.31±5.77) and (48.15±5.18) ng·mL^-1; the IL-1β levels were (28.15±4.68), (36.83±6.97), (40.18±4.40) and (19.15±2.67) pg·mL^-1; the TNF-α levels were (281.15±25.15), (324.06±16.85), (337.08±23.11) and (219.06±27.68) pg·mL^-1; the integrated optical density of Brdu were 1.70±1.19, 0.89±0.12, 0.93±0.14 and 2.14±0.15; the relative expression levels of miRNA-let-7d were 2.02±0.18, 2.67±0.54, 2.88±0.30 and 1.11±0.16; the relative expression levels of NR2E1 mRNA were 2.87±0.39, 0.96±0.09, 1.07±0.12 and 3.29±0.35; the relative expression levels of SIRT1 mRNA were 1.62±0.37, 0.99±0.08, 1.04±0.10 and 2.30±0.34, respectively. Compared with the model group, the above indexes in experimental group have statistical significance (all P<0.05).

The overexpression of NR2E1 receptor in isolated nucleus may protect the dentate gyrus nerve regeneration in diabetic rats with depression by regulating miRNA-let-7d/TLX/SIRT1 signal transduction.