To investigate the neuroprotective effect and mechanism of liraglutide on diabetic rats.

24 healthy male SPF Goto-Kakizaki (GK) rats with random blood glucose greater than 11.1 mmol/L were selected as the experimental group, and randomly divided into diabetes mellitus group (n=12) and liraglutide group (n=12). Ten healthy male SPF Wistar rats with the same age and weight as GK rats were selected as normal control group. After adaptively feeded for 2 weeks, the liraglutide group was given liraglutide (400 μg·kg^-1·d^-1, subcutaneous injection), while the control group and diabetes mellitus group were given the same volume of saline, and continued to be administered for 8 weeks. After 10 weeks, data and biochemical indicators were recorded. Effects of liraglutide on learning and memory in diabetes mellitus rats were detected by Morris water maze test. HE staining observed the hippocampal neurons morphology. Western blotting method detected the expression of p- IκB kinase (IKK)β, p-NF-κB, NF-κB, Klotho, and PRX2 in hippocampus.

Morris water maze test showed that liraglutide can improve the spatial learning and memory ability of diabetes mellitus rats. HE staining showed that liraglutide significantly reduced the pathological damage of hippocampal neurons of diabetes mellitus rats. Western blotting showed that liraglutide inhibited NF-κB signaling pathway in hippocampus of diabetes mellitus rats. The expression of Klotho protein in hippocampus of diabetes mellitus group was significantly lower than that of control group, while the expression of PRX2 protein was higher than control group (t=8.298, -7.398, all P<0.01). The expression of Klotho and PRX2 protein in hippocampus of liraglutide group were higher than diabetes mellitus group (t=-13.059, 14.113, all P<0.01). The expression of Klotho protein of liraglutide group was similar to that of control group (t=-1.137, P>0.05). The expression of PRX2 protein was significantly higher than control group (t=-28.055, P<0.01).

Liraglutide may enhance the expression of antioxidant stress protein including Klotho and PRX2, by inhibiting NF-κB signaling pathway in hippocampus of diabetes mellitus rats, reduced oxidative stress and improved the injury of hippocampal neuronal in diabetes mellitus rats, which seems to play a neuroprotective effect, to prevent and delay the occurrence of diabetic encephalopathy. (Chin J Endocrinol Metab, 2018, 34: 509-515)

Liraglutide; Diabetic encephalopathy; Hippocampal neurons; Nuclear factor-κB signaling pathway; Klotho; Peroxiredoxin 2