ABSTRACT
Objective:To evaluate the effect of hydrogen on activation of A1 astrocytes in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:A total of 164 clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=41 each) using a random number table method: sham operation group (group Sham), sham operation plus hydrogen group (group Sham+ H 2), group SAE and SAE plus hydrogen group (group SAE+ H 2). The SAE model was established by cecal ligation and perforation.Group Sham+ H 2 and group SAE+ H 2 inhaled 2% hydrogen starting from 1 and 6 h after operation, respectively.Twenty mice in each group were selected to observe the 7-day survival rate after operation.The remaining mice were sacrificed at 12 h after operation, and brain tissues were removed for examination of the pathological changes in hippocampal CA1 region (with a light microscope) and for determination of the apoptosis in neurons (by TUNEL), co-expression of hippocampal glial fibrillary acidic protein (GFAP) and complement C3 (by immunofluorescence staining), expression of A1 astrocyte marker C3 (by Western blot), and contents of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high-mobility group box 1 protein (HMGB1) (by enzyme-linked immunosorbent assay). The abnormal cell ratio and apoptosis rate were calculated.Six mice in each group were selected at 7 days after operation to perform Y-Maze paradigm. Results:Compared with group Sham, the 7-day survival rate after operation was significantly decreased, the abnormal cell ratio and apoptosis rate of hippocampal neurons were increased, the contents of TNF-α, IL-6 and HMGB1 were increased, the expression of C3 was up-regulated, the number of cells coexpressing GFAP and C3 was increased, the exploration time spent in the novel arm in Y-Maze paradigm was shortened, and the preference index was decreased in group SAE ( P<0.05). Compared with group SAE, the 7-day survival rate after operation was significantly increased, the abnormal cell ratio and apoptosis rate of hippocampal neurons were decreased, the contents of TNF-α, IL-6 and HMGB1 were decreased, the expression of C3 was down-regulated, the number of cells coexpressing GFAP and C3 was decreased, the exploration time spent in the novel arm in Y-Maze paradigm was prolonged, and the preference index was increased in group SAE+ H 2 ( P<0.05). There was no significant difference in each parameter mentioned above between Sham group and Sham+ H 2 group ( P>0.05). Conclusion:The mechanism by which hydrogen improves SAE may be related to inhibiting activation of A1 type astrocytes in mice.
ABSTRACT
Hedgehog pathway is an osteogenesis-related signaling pathway . During embryonic development , it regulates the growth and proliferation of progenitor cells and tissue formation. This pathway can be activated during liver injury. Activated Hedge-hog signaling pathway is involved in many aspects of liver wound-healing responses, including hepatic progenitor cell pro-liferation, myofibroblast transdifferentiation, apoptosis of various types of liver cells, inflammatory reactions, and vascular remod-eling. This article reviews the research progress in the role of Hedgehog signaling pathway in liver injury and the underlying mechanisms. The potential drug targets are also discussed. This review is to provide novel insights into antifibrotic research and therapeutic targets.
