Effect of hydrogen on expression of matrix metalloproteinase-9 in brain tissues of mice with sepsis-associated encephalopathy / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of hydrogen on the expression of matrix metalloproteinase-9 (MMP-9) in brain tissues of mice with sepsis-associated encephalopathy (SAE).Methods A total of 212 clean-grade healthy male C57BL/6J mice,aged 6-8 weeks,weighing 20-25 g,were divided into 4 groups (n =53 each) using a random number table method:sham operation group (group Sham),sham operation plus hydrogen group (group Sham+H2),group SAE and SAE plus hydrogen group (group SAE+ H2).The sepsis model was established by intraperitoneally injecting human fecal suspension.Sham+H2 and SAE+H2 groups inhaled 2％ hydrogen for 1 h at 1 and 6 h after establishing the model,respectively.Postoperative 14-day survival rate was recorded.Evans blue (EB) was injected into the tail vein at 24 h after establishing the model,and the content of EB in brain tissues was calculated.Brain tissues were taken for determination of brain water content.The expression of tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6) and high-mobility group box 1 protein (HMGB1) in hippocampal tissues was detected by enzymelinked immunosorbent assay.The expression of MMP-9 and ZO-1 protein and mRNA in hippocampal tissues was determined by Western blot and real-time polymerase chain reaction,respectively,at 6,12 and 24 h after establishing the model.Results Compared with Sham group,the 14-day survival rate was significantly decreased,the EB content in brain tissues,brain water content,and contents of TNF-α,IL-6 and HMGB1 were significantly increased,the expression of MMP-9 protein and mRNA was up-regulated,and the expression of ZO-1 protein and mRNA was down-regulated in SAE and SAE+H2 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group Sham+H2 (P＞0.05).Compared with group SAE,the 14-day survival rate was significantly increased,the EB content in brain tissues,brain water content,and contents of TNF-α,IL-6 and HMGB1 were significantly decreased,the expression of MMP-9 protein and mRNA was down-regulated,and the expression of ZO-1 protein and mRNA was up-regulated in group SAE+H2 (P＜0.05).Conclusion The mechanism by which hydrogen attenuates the blood-brain barrier damage may be related to inhibiting MMP-9 expression and to reducing inflammatory responses in brain tissues of SAE mice.