Effects of hydrogen sulfide on cognitive dysfunction and NR2B in rats.
Hepatic ischemia/reperfusion (hepatic I/R) has been found to induce cognitive dysfunction. The NR2B subunit of N-methyl-D-aspartate (NMDA) receptors is a major factor in memory and learning processes, and hydrogen sulfide (H2S) may modulate this NMDA receptor. Therefore, in this study, sodium hydrosulfide (NaHS, a donor of H2S) was administered in an animal model of hepatic I/R to investigate the effects of H2S on cognitive impairment and expression of NR2B.



NaHS (5 mg/kg) or normal saline was administered intraperitoneally once a day for 11 consecutive days, during which a rat model of 70% hepatic I/R was established on the fourth day. Cognitive function was evaluated using a Morris water maze, mRNA and protein levels of the NR2B subunit were detected in the hippocampus by RT-PCR and Western blotting. All these tests were performed on postoperative days 1, 3, 5, and 7.



Cognitive dysfunction was detected in the hepatic I/R group, and this dysfunction was associated with a decrease in the mRNA and protein levels of the NR2B subunit of the NMDA receptors in the hippocampus. In contrast, treatment with NaHS significantly ameliorated the impairment of cognitive function caused by hepatic I/R, and an increase in mRNA and protein levels of the NR2B subunit was detected in the corresponding hippocampus tissues.



The present data suggest that H2S exerts a protective effect on hepatic I/R-induced cognitive impairment, and this effect may be associated with the NR2B subunit of the NMDA receptors. H2S may represent a novel therapeutic agent for the treatment of postoperative cognitive dysfunction after liver surgery.
Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Fa-Ping
FP
Tu
Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Jun-Xiang
JX
Li
Hepatobiliary Research Institute of North Sichuan Medical College, Nanchong, China.
Qiang
Q
Li
Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China. Electronic address: wangjinsmc@sina.com.
Ji
J
Wang
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008107:Liver Diseases / Q000150:complications*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D015415:Biomarkers; C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013440:Sulfides; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
Cognitive dysfunction; Hepatic ischemia/reperfusion; Hydrogen sulfide; NR2B