Tu Fa-Ping, Li Jun-Xiang, Li Qiang, Wang Ji
Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Hepatobiliary Research Institute of North Sichuan Medical College, Nanchong, China.
J Surg Res. 2016 Oct;205(2):426-431. doi: 10.1016/j.jss.2016.06.071. Epub 2016 Jul 5.
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.
已发现肝脏缺血/再灌注（肝缺血/再灌注）可诱发认知功能障碍。N-甲基-D-天冬氨酸（NMDA）受体的NR2B亚基是记忆和学习过程中的一个主要因素，而硫化氢（H₂S）可能调节该NMDA受体。因此，在本研究中，在肝缺血/再灌注动物模型中给予硫氢化钠（NaHS，一种H₂S供体），以研究H₂S对认知障碍及NR2B表达的影响。
每天腹腔注射一次NaHS（5mg/kg）或生理盐水，连续注射11天，在此期间，于第4天建立70%肝缺血/再灌注大鼠模型。使用Morris水迷宫评估认知功能，通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测海马中NR2B亚基的mRNA和蛋白质水平。所有这些检测均在术后第1、3、5和7天进行。
在肝缺血/再灌注组中检测到认知功能障碍，且这种功能障碍与海马中NMDA受体NR2B亚基的mRNA和蛋白质水平降低有关。相比之下，NaHS治疗显著改善了肝缺血/再灌注引起的认知功能损害，并且在相应的海马组织中检测到NR2B亚基的mRNA和蛋白质水平升高。
目前的数据表明，H₂S对肝缺血/再灌注诱导的认知障碍具有保护作用，且这种作用可能与NMDA受体的NR2B亚基有关。H₂S可能是一种治疗肝脏手术后术后认知功能障碍的新型治疗药物。
