Effect of hydrogen on Nrf2∕HO?1 signaling pathway 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 nuclear factor erythroid 2?related factor 2(Nrf2)∕heme oxygenase?1(Nrf2∕HO?1)signaling pathway in brain tissues of mice with sepsis?associat?ed encephalopathy. Methods Ninety adult male ICR mice, weighing 20-25 g, were divided into 3 groups(n=30 each)using a random number table sham operation group(group SH), sepsis?associated encephalopathy group(group SAE)and sepsis?associated encephalopathy plus hydrogen group(group SAE+H). Sepsis was produced by cecum ligation and puncture(CLP). Hydrogen?rich normal saline 10 ml∕kg was injected intraperitoneally at 1 and 3 h after CLP in group SAE+H. At 24 h after CLP, tissues in hippocampal CA1 area were obtained for calculation of the density of dendritic spine(using Golgi staining) and for microscopic examination of apoptosis in nerve cells(by TUNEL). Apoptotic index(AI)was cal?culated. At 6, 12 and 24 h after CLP, the expression of Nrf2 in hippocampal nucleoprotein(N?Nrf2), HO?1 in total protein and high?mobility group box 1 protein(HMGB1)was detected by Western blot, and the expression of HMGB1 mRNA was determined by real?time polymerase chain reaction. Results Com?pared with group SH, the density of dendritic spines and AI in hippocampal CA1 area were significantly in?creased, and the expression of hippocampal N?Nrf2, HO?1, HMGB1 protein and mRNA was up?regulated in SAE and SAE+H groups(P<0.05). Compared with group SAE, the density of dendritic spines and AI in hippocampal CA1 area were significantly decreased, the expression of hippocampal N?Nrf2 and HO?1 was up?regulated, and the expression of HMGB1 protein and mRNA was down?regulated in group SAE+H(P<0.05). Conclusion The mechanism by which hydrogen reduces sepsis?associated encephalopathy may be related to activating Nrf2∕HO?1 signaling pathway in brain tissues of mice.