Chen Di, Pan Hao, Li Chunwen, Lan Xiucai, Liu Beibei, Yang Guangtian
Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Emergency, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
J Huazhong Univ Sci Technolog Med Sci. 2011 Oct;31(5):632. doi: 10.1007/s11596-011-0573-2. Epub 2011 Oct 25.
To investigate the interaction and involvement of sodium hydrosulfide (NaHS), a H(2)S 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 H(2)S formation) group. The four groups were observed at 3, 6, 9, 12 h after treatment. We examined hippocampal H(2)S synthesis and the expression of cystathionine-β-synthetase (CBS), a major enzyme involved in the H(2)S 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, H(2)S 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 H(2)S can increase injurious effects and treatment with AOAA can protect the brain from injury.
为研究硫化氢供体硫氢化钠（NaHS）对脓毒症相关性脑病大鼠海马体的相互作用及影响，对大鼠进行盲肠结扎穿孔（CLP）诱导的脓毒症实验。将成年雄性Sprague-Dawley大鼠随机分为四组：假手术组、CLP组、CLP+NaHS组和CLP+氨基氧乙酸（AOAA，一种硫化氢生成抑制剂）组。于治疗后3、6、9、12小时观察这四组大鼠。检测海马体中硫化氢的合成及胱硫醚-β-合成酶（CBS，海马体中参与硫化氢合成的主要酶）的表达。采用逆转录聚合酶链反应（RT-PCR）检测CBS表达。运用酶联免疫吸附测定（ELISA）法测定海马体中炎性细胞因子（TNF-α、IL-1β）的浓度。通过海马体组织学检查研究神经元损伤情况。与假手术组相比，CLP组海马体中硫化氢合成显著增加，且在CLP后3小时达到峰值（P<0.05）。脓毒症还导致海马体中CBS mRNA显著上调。海马体中TNF-α和IL-1β水平在各测量时间点均显著升高（P<0.05），且在约3小时时也达到峰值。给予NaHS显著加重了脓毒症相关性海马体炎症，这可通过TNF-α和IL-1β活性以及海马体组织学变化得以证明。在AOAA预处理的脓毒症大鼠中，脓毒症相关性海马体炎症减轻。研究得出结论，脓毒症大鼠可能会遭受脑损伤，促炎细胞因子升高是该过程的原因。此外，给予硫化氢会增加损伤作用，而用AOAA治疗可保护大脑免受损伤。
