Effect of hydrogen on mitochondrial dynamics 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 dynamics in hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:A total of 224 clean-grade healthy male C57 mice, weighing 20-25g, aged 6-8 weeks, were divided into 4 groups ( n=56 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H 2), SAE group and SAE + hydrogen group (group SAE+ H 2). Sepsis was produced by cecum ligation and puncture (CLP). Sham+ H 2and SAE+ H 2 groups inhaled 2% hydrogen for 1 h starting from 1 and 6 h after CLP, respectively.The postoperative 7-day survival rate was recorded.Brain tissues were obtained at 24 h after operation for examination of the pathological changes in hippocampal CA1 region (with a light microscope) and for determination of mitochondrial membrane potential (MMP) (by fluorescence spectrophotometry) and ATP content (by a bioluminescence assay) in hippocampal tissues.At 6, 12 and 24 h after operation, hippocampal mitochondria were isolated for determination of the expression of dynamin-related protein 1 (Drp1) and the mitochondrial fusion proteins mitofusin 2 (Mfn2) (by Western blot). Results:Compared with group Sham, the postoperative 7-day survival rate was significantly decreased, the contents of MMP and ATP were decreased, the expression of Drp1 was up-regulated, and the expression of Mfn2 was down-regulated( P<0.05), the pathological changes were aggravated in hippocampal CA1 region in SAE and SAE+ H 2 groups, and no significant change was found in the parameters mentioned above in group Sham+ H 2 ( P>0.05). Compared with group SAE, the postoperative 7-day survival rate was significantly increased, the contents of MMP and ATP were increased, the expression of Drp1 was down-regulated, and the expression of Mfn2 was up-regulated( P<0.05), the pathological changes were attenuated in hippocampal CA1 region in group SAE+ H 2. Conclusion:The mechanism by which hydrogen improves mitochondrial function is probably associated with promoting mitochondrial fusion and inhibiting mitochondrial fission in hippocampus of mice with SAE.