Role of Toll-like receptor 4 in mechanical ventilation-induced activation of microglias in hippocampi of mice
10.3760/cma.j.issn.0254-1416.2017.05.015
- VernacularTitle:Toll样受体4在机械通气致小鼠海马小胶质细胞活化中的作用
- Author:
Yufeng ZOU
;
Chang CHEN
;
Ting CHEN
;
Zongze ZHANG
;
Mian PENG
;
Yanlin WANG
- Keywords:
Toll like receptor 4;
Respiration,artificial;
Hippocampus;
Microglia
- From:
Chinese Journal of Anesthesiology
2017;37(5):569-572
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of Toll-like receptor 4 (TLR4) in mechanical ventilation-induced activation of microglias in the hippocampi of mice.Methods Forty-two healthy male TLR4 gene knocked out C57BL/10ScNJNju mice and 42 wild type C57BL/6 mice,aged 10-12 weeks,weighing 20-25 g,were used in the study.The mice of either group were divided into 2 subgroups (n =21 each) using a random number table:spontaneous breathing subgroup (subgroup SB) and mechanical ventilation subgroup (subgroup MV).In subgroup SB,the mice were exposed to isoflurane for 6 h in an anesthesia chamber.After tracheal intubation,the mice were mechanically ventilated for 6 h when anesthesia was maintained with isoflurane in subgroup MV.Twelve mice were selected from each subgroup at 1 and 3 days after ventilation,fear conditioning test was performed to assess the cognitive function,and the rate of freezing time was recorded.Three mice in each subgroup were sacrificed at 1 day after ventilation,and the brains were removed to observe the morphological changes of microglias (by double immunofluorescent staining) and to count CD11b positive cells and co-expression of TLR4 with CD11b (TLR4/CD11b) positive cells in hippocampal microglias.Six mice in each subgroup were sacrificed at 1 day after ventilation,and the hippocampi were isolated for determination of the content of tumor necrosis factor-alpha (TNF-α) in hippocampal tissues by enzyme-linked immunosorbent assay.Results Compared with subgroup SB of wild type group,the rate of freezing time was significantly decreased at 1 and 3 days after ventilation,and the number of CD1 1b positive cells and TLR4/CD1 1b positive cells were increased,and the content of TNF-α was increased in subgroup MV of wild type group (P＜0.05),and the number of CD1 1b positive cells and content of TNF-α were significantly increased in subgroup MV of geue knockout group (P＜0.05).Compared with subgroup SB of gene knockout group,the rate of freezing time was significantly decreased at 1 and 3 days after ventilation,and the number of CD1 1b positive cells and content of TNF-α were increased in subgroup MV of gene knockout group (P＜0.05).Compared with subgroup MV of wild type group,the rate of freezing time was significantly increased at 1 and 3 days after ventilation,and the number of CD11b positive cells and content of TNF-α were decreased in subgroup MV of gene knockout group (P＜0.05).Conclusion The mechanism by which mechanical ventilation induces activation of microglias in hippocampi is partially related to TLR4 in mice.
