Effects of hydrogen sulfide on spatial learning and memory and oxidative stress in hippocampus tissue of diabetic rat

Objective To investigate the effects of hydrogen sulfide (H₂S) on spatial learning and memory in diabetic rats, and explore the underlying mechanism.

Methods Male rats were randomly divided into normal (CON) group, diabetes mellitus (STZ) group, diabetes+sodium hydrosulfide (NaHS) (SH) group, and normal+NaHS (CH) group, with 8 rats in each group.Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin.Four weeks after successfully making the model, rats in SH group and CH group were intraperitoneally injected with 56 μmol/kg NaHS solution once a day.After treatment for 4 weeks, the fasting blood glucose (FBG) and body weight (BW) were measured.Spatial learning and memory abilities including escape latency, time spent in the target quadrant, and escape latency to the target quadrant were assessed by Morris water maze.The morphology of hippocampus tissue was observed by HE staining.The levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in hippocampus tissue were determined by the kits.The mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in hippocampus tissue were detected using real time-quantitative polymerase chain reaction.

Results Compared with the CON group, there was no significant difference in the various indexes in the CH group (P>0.05).In the STZ group, the escape latency and escape latency to the target quadrant were extended, and the time spent in the target quadrant was shortened (P < 0.01).The histological structure of hippocampus tissue was obviously damaged.The levels of FBG and MDA were increased (P < 0.01), whereas BW, the levels of T-AOC, SOD, GSH-Px activity, and Nrf2, HO-1 mRNA expression were decreased, the difference of which was statistically significant (P < 0.01).Compared with the STZ group, except for FBG, the above indicators were markedly improved in the SH group (P < 0.05 to P < 0.01).

Conclusions H₂S attenuates cognitive dysfunction in diabetic rats, the mechanism of which might be associated with the inhibition of oxidative stress and up-regulation of the Nrf2/HO-1 pathway in hippocampus tissue.