Abstract: Objective To investigate the effect and mechanism of silencing latent transforming growth factor beta binding protein 2 (LTBP2) gene on learning and memory function of diabetic rats. Methods Forty-five male SD rats were given a single intraperitoneal injection of streptozotocin (STZ) at 55 mg/kg, and blood glucose was collected from the tail vein at 72 hours. Rats with a blood glucose concentration greater than 16.7 mmol/L were designated as diabetes model rats. After the model was successfully induced, the rats were randomly divided into 3 groups: diabetes group (DM), si-LTBP2 group (the hippocampus of rats was given 10 μL adenovirus packaged siRNA targeting LTBP2) and sc-LTBP2 group (the rats were given LTBP2 control sequence 10 μL in hippocampus). Another 15 normal rats were used as control group (CON group). After 12 weeks, the learning and memory ability were detected by water maze, the expression of hippocampal LTBP2 was detected by immunohistochemical staining and the relative expressions of hippocampal LTBP2, Toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) protein were detected by Western blot assay. The apoptosis of hippocampal neurons was detected by TUNEL staining. Results Compared with the CON group, the expressions of LTBP2, TLR4 and NF-κB were significantly increased in the DM group and the sc-LTBP2 group. The apoptosis of hippocampal neurons was significantly increased, and the learning and memory ability of rats was significantly decreased (all P＜0.05). Compared with the DM group, the expression levels of LTBP2, TLR4 and NF-κB were significantly reduced, the apoptosis of hippocampal neurons was significantly reduced, and the learning and memory ability of rats was significantly improved in the si-LTBP2 group (all P＜0.05). Conclusion Silencing the expression of LTBP2 in the hippocampus can significantly improve the learning and memory ability of diabetic rats, and its mechanism may be related to the inhibition of the TLR4/NF-κB signaling pathway.

Key words: diabetes mellitus, type 1, Toll-like receptor 4, NF-kappa B, apoptosis, learning, memor, latent transforming growth factor beta binding protein 2, TLR4/NF-kappa B signaling pathway