Hydrogen Sulfide Inhibits Oxidative Stress And Apoptosis And Up-regulates SIRT-1 Expression In The Hippocampus Of Streptozotocin-induced Diabetic Rats

[Background and Objective] Diabetes mellitus(DM) is one of the main diseases affecting human health. Both oxidative stress and apoptosis play major roles in the pathogenesis of diabetic brain damage. Hydrogen sulfide(H2S), the third gaseous mediator, is a novel signaling molecule in brain and possesses the anti-oxidative role and anti-apoptotic effect. Silent information regulator 1(Sirt-1) produces anti-oxidative and anti-apoptotic effects though different signaling pathway. In addition, our team recently found that H2 S up-regulates the expression of Sirt-1 in neuronal cells. Thus, we hypothesized that H2 S attenuates oxidative stress and apoptosis in the hippocampus of diabetic rats, which is involved in up-regulating Sirt-1. To test the hypothesis, the SD(Sprague-Dawley) rats were treated with streptozotocin(STZ) to induce diabetes and explored whether H2 S antagonizes oxidative stress and apoptosis in the happocampus of diabetic rats and whether up-regulation of Sirt-1 is involved in this protective role. [Methods] The levels of malondialdehyde(MDA), 4-hydroxynonenal(4-HNE) and reduced glutathione(GSH) in the happocampus were determined by enzyme-linked immunosorbent assay(ELISA). The viability of superoxide dismutase(SOD) in the happocampus was assayed by NBT assay. Western blotting was used to evaluate the protein expressions of Sirt-1, Bcl-2(B-cell lymphoma-2) and caspase-3. [Results] We found that H2 S significantly reduced the levels of MDA and 4-HNE and elevated the levels of SOD and GSH in the happocampus of STZ-induced diabetic rats. H2 S attenuated STZ-induced decrease in the expression of hippocampal Bcl-2 and increase in the expression of hippocampal caspase-3. We also found a significant reduction of Sirt-1 in the happocampus of STZ-induced diabetic rats, which was reversed to near normal values by treatment with Na HS(30,100 μmol/kg/d, ip). [Conclusion] H2 S inhibits oxidative stress and apoptosis in the hippocampus of STZ-induced diabetic rats, which may be involved in up-regulation of happocampal sirt-1.