摘要
To investigate the interaction and involvement of sodium hydrosulfide （NaHS）, a H2S donor, on hippocampus of rats suffering from sepsis-associated encephalopathy, rats were subjected to cecal ligation and puncture （CLP）-induced sepsis. Adult male Sprague-Dawley rats were randomly divided into four groups： Sham group, CLP group, CLP＋NaHS group and CLP＋aminooxyacetic acid （AOAA, an inhibitor of H2S formation） group. The four groups were observed at 3, 6, 9, 12 h after treatment. We examined hippocampal H2S synthesis and the expression of cystathionine-β-synthetase （CBS）, a major enzyme involved in the H2S synthesis in hippocampus. CBS expression was detected by reverse transcription polymerase chain reaction （RT-PCR）. The concentrations of inflammatory cytokines （TNF-α, IL-1β） were determined in hippocampus by using enzyme-linked immunosorbent assay （ELISA）. Neuronal damage was studied by histological examination of hippocampus. In CLP group, H2S synthesis was significantly increased in hippocampus compared with sham group and it peaked 3 h after CLP （P〈0.05）. Sepsis also resulted in a significantly upregulated CBS mRNA in hippocampus. The levels of TNF-α and IL-1β in the hippocampus were substantially elevated at each time point of measurement （P〈0.05）, and they also reached a peak value at about 3 h. Administration of NaHS significantly aggravated sepsis-associated hippocampus inflammation, as evidenced by TNF-α and IL-1β activity and histological changes in hippocampus. In septic rats pretreated with AOAA, sepsis-associated hippocampus inflammation was reduced. It is concluded that the rats subjected to sepsis may suffer from brain injury and elevated pro-inflammatory cytokines are responsible for the process. Furthermore, administration of H2S can increase injurious effects and treatment with AOAA can protect the brain from injury.
To investigate the interaction and involvement of sodium hydrosulfide （NaHS）, a H2S donor, on hippocampus of rats suffering from sepsis-associated encephalopathy, rats were subjected to cecal ligation and puncture （CLP）-induced sepsis. Adult male Sprague-Dawley rats were randomly divided into four groups： Sham group, CLP group, CLP＋NaHS group and CLP＋aminooxyacetic acid （AOAA, an inhibitor of H2S formation） group. The four groups were observed at 3, 6, 9, 12 h after treatment. We examined hippocampal H2S synthesis and the expression of cystathionine-β-synthetase （CBS）, a major enzyme involved in the H2S synthesis in hippocampus. CBS expression was detected by reverse transcription polymerase chain reaction （RT-PCR）. The concentrations of inflammatory cytokines （TNF-α, IL-1β） were determined in hippocampus by using enzyme-linked immunosorbent assay （ELISA）. Neuronal damage was studied by histological examination of hippocampus. In CLP group, H2S synthesis was significantly increased in hippocampus compared with sham group and it peaked 3 h after CLP （P〈0.05）. Sepsis also resulted in a significantly upregulated CBS mRNA in hippocampus. The levels of TNF-α and IL-1β in the hippocampus were substantially elevated at each time point of measurement （P〈0.05）, and they also reached a peak value at about 3 h. Administration of NaHS significantly aggravated sepsis-associated hippocampus inflammation, as evidenced by TNF-α and IL-1β activity and histological changes in hippocampus. In septic rats pretreated with AOAA, sepsis-associated hippocampus inflammation was reduced. It is concluded that the rats subjected to sepsis may suffer from brain injury and elevated pro-inflammatory cytokines are responsible for the process. Furthermore, administration of H2S can increase injurious effects and treatment with AOAA can protect the brain from injury.
基金
supported by a grant from the National Natural Sciences Foundation of China (No. 81071526)
