H₂S Prevents Chronic Unpredictable Mild Stress（CUMS）-induced Hippocampal Oxidative Stress By Up-regulating BDNF-TrkB Pathway

[Background and Objective]Chronic unpredictable mild stress(CUMS) can induce the damage of nerve cells in the hippocampus. Hydrogen sulfide(H2S) has neuroprotective function. Brain-derived neurotrophic factor(BDNF) can promote the neuron survival and proliferation and protect nerve damage through its receptor-Tropomyosin receptor kinase B(Trk B).Our laboratory has proved the protective role of H2 S against CUMS-caused endoplasmic reticulum stress. Wether can H2 S protect CUMS-caused hippocampal oxidative stress and BDNF-Trk B pathway mediates this effect of H2S? Therefore, this work is to explore the protective effect of H2 S on CUMS-induced oxidative stress in hippocampus and its mechanisms. [Methods]A chronic stress model was established by CUMS. The contents of 4-Hydroxynonenal(4-HNE), malondialdehyde(MDA), and glutathione(GSH) in the hippocampal tissue were detected by Enzyme linked immunosorbentassay(ELISA). The activty of super oxide dismutase(SOD) was examined by nitrobluetetrazolium(NBT) assay. The expressions of BDNF and Trk B protein in hippocampus were tested by Western-blotting. [Results]1. H2S(30, 100 μmol/kg/d) reduced the contents of MDA, 4-HNE, while increased the levels of GSH and the activity of SOD in the hippocampus of CUMS rats, which indicated that H2 S prevents CUMS-induced hippocampal oxidative stress. 2. H2S(30, 100 μmol/kg/d) increased the expressions of BDNF and Trk B protein in the hippocampus of CUMS-treated rats. 3. K252a(the blocker of Trk B receptor, 1 μg/d) abolished H2S(30, 100 μmol/kg/d)-suppressed the contents of MDA and 4-HNE and-increased GSH content and SOD activity in the hippocampus of CUMS-treated rats. [Conclusion] H2 S prevents CUMS-caused hippocampal oxidative stress by up-regulating the pathway of BDNF-Trk B.