Effect of hydrogen on mitochondrial biosynthesis in hippocampus of mice with sepsis-associated encephalopathy / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of hydrogen on mitochondrial biosynthesis in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Method Two hundred and twenty-four healthy clean-grade male C57BL/6J mice,aged 6-8 weeks,weighing 20-25 g,were divided into 4 groups (n=56 each) using a random number table method:sham operation group (group SH),sham operation plus hydrogen group (group SH+H2),group SAE,and SAE plus hydrogen group (group SAE+H2).The model of SAE was established by cecal ligation and puncture in anesthetized mice.Group SH+H2 and group SAE+H2 inhaled 2％ hydrogen for 1 h starting from 1 and 6 h after operation,respectively.Twenty mice were selectde to record the postoperative 7-day survival rate.The remaining animals were sacrificed at 24 h after operation,and brain tissues were taken for examination of the pathological changes in hippocampal CA1 region (with a light microscope) and for determination of neuronal apoptosis (by TUNEL),mitochondrial membrane potential (MMP) (by fluorescence spectrophotometry) and ATP content (by a bioluminescence assay).The apoptosis rate was calculated.The expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in hippocampus was determined by Western blot at 6,12 and 24 h after operation.Results Compared with group SH,the postoperative 7-day survival rate was significantly decreased,the apoptosis rate of hippocampal neurons was increased,the contents of MMP and ATP were decreased,and the expression of PGC-1α was up-regulated in SAE and SAE+H2groups (P＜0.05),and no significant change was found in the parameters mentioned above in group SH+H2 (P＞0.05).Compared with group SAE,the postoperative 7-day survival rate was significantly increased,and the apoptosis rate of hippocampal neurons was decreased,the contents of MMP and ATP were increased,and the expression of PGC-1α was up-regulated (P＜0.05),and the pathological changes of hippocampal tissues were significantly attenuated in group SAE+H2.Conclusion The mechanism by which hydrogen mitigates SAE may be related to promoting mitochondrial biosynthesis in mice.