Effects of hydrogen sulfide on a rat model of sepsis-associated encephalopathy.
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.
Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Di
D
Chen
Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Hao
H
Pan
Department of Emergency, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Chunwen
C
Li
Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Xiucai
X
Lan
Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Beibei
B
Liu
Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. guangtiany@hotmail.com.
Guangtian
G
Yang
D000625:Aminooxyacetic Acid / Q000627:therapeutic use*; D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy* / Q000209:etiology; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications*
D016207:Cytokines; D018696:Neuroprotective Agents; D000625:Aminooxyacetic Acid; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide