1.Effects and mechanism of methionine restriction on macrophage for lipopolysaccharide-induced acute lung injury in mice
Xianjian LIAO ; Jing WEN ; Jiaxiang DUAN ; Lunli XIANG ; Zhen YANG ; Qingying HE ; Jiaolin NING
Journal of Army Medical University 2024;46(7):688-694
Objective To investigate the effects of methionine restriction(MR)on macrophages in lipopolysaccharide(LPS)-induced acute lung injury(ALI)and to explore the underlying mechanism.Methods According to the random number table method,36 male C57BL/6J mice(6~8 weeks old,23±2 g)were divided into 3 groups with 12 mice in each group:the sham group,the LPS group and the LPS+MR group.HE staining and pathological scoring of lung injury were performed in lung tissues.The expression of LPS-binding protein(LBP)and Toll-like receptor-4(TLR4)was detected by RT-qPCR and Western blotting.Macrophage-colony stimulating factor(M-CSF),granulocyte-macrophage-colony stimulating factor(GM-CSF)and chemokine C-C motif ligand 3(CCL3)which are all macrophage-associated chemokines were analyzed by immunohistochemistry.Results Compared with the sham group,the pathological score of lung injury in the LPS group was significantly increased(P<0.01);The mRNA and protein expression levels of LBP and TLR4 were significantly increased;The number of positive cells of CD11b,F4/80,M-CSF,GM-CSF and CCL3 were significantly increased(P<0.01).MR significantly improved LPS-induced ALI,and decreased the pathological score of lung injury(P<0.01);The mRNA and protein expression levels of LBP and TLR4 were decreased;Compared with the LPS group,the number of positive cells of CD11 b,F4/80,M-CSF,GM-CSF and CCL3 were reduced in the LPS+MR group(P<0.01).Conclusion MR could attenuate LPS-induced ALI by inhibiting the expression of macrophage chemokines and preventing infiltration and activation of macrophage to lungs.
2.Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude
Qingying HE ; Yue LI ; Jing WEN ; Lunli XIANG ; Jiaxiang DUAN ; Xianjian LIAO ; Bin YI ; Jiaolin NING
Journal of Army Medical University 2024;46(20):2352-2359
Objective To investigate the impact and mechanism of efaproxiral (RSR13),a hemoglobin allosteric agent,on lung injury in rats caused by explosion-induced shock waves in plateau areas. Methods Eighty-two healthy male SD rats (8-week-old,transferred from an altitude of 2 880 m to 4700 m within 6 h)were randomly divided into blast injury group and RSR13+blast injury group (intraperitoneal injection of 150 mg/kg RSR132 h before explosion).Sixty rats were positioned at 5 m from the explosion source and divided into 5-m blast injury group (n=30)and 5-m RSR13+blast injury group (n=30). Additionally,16 rats were positioned at 6 m from the explosion source and then assigned into 6-m blast injury group (n=8)and 6-m RSR13+blast injury group (n=8).The left 6 rats served as control (n=6).Survival outcomes of each rat group positioned 5 m from the explosion source were observed over a 24-hour period.HE staining was used to evaluate the pathological score of the surviving rats positioned at 6 m from the explosion source in 24 h after explosion,along with arterial blood gas analysis.The contents of glutathione (GSH),malondialdehyde (MDA ) and superoxide dismutase (SOD ) in the lung tissues were determined by colorimetry.Western blotting was conducted to measure the expression levels of cleaved caspase-3 and occludin in the lung tissue.Results RSR13 pretreatment increased the survival rate immediately after explosion (93.3% vs 46.7%,P<0.01 )and at 1 h after explosion (86.7% vs 46.7%,P<0.01 )in plateau areas of 5 m from the explosion source.At high altitude,RSR13 pretreatment reduced the pathological score of lung injury in rats 6 m away from the explosion source (8.27±0.93 vs 13.70±0.78,P<0.01 ),but had no significant effect on the results of arterial blood gas analysis in rats with lung blast injury (P>0.05 ).In addition,RSR13 pretreatment also increased GSH content (40.27±12.47 vs 22.62±10.88 μg/g,P<0.05),but showed no obvious effect on MDA content and SOD activity (P>0.05 ),decreased the protein level of cleaved caspase-3 (P<0.01 )and increased that of occludin (P<0.05 )in the lung tissues.Conclusion RSR13 exerts significant protective effect on lung injury in rats caused by explosion-induced shock waves in high-altitude environment,which may be related to its increasing antioxidant capacity,reducing cell apoptosis and decreasing barrier permeability of lung ventilation.
3.Effects of biorhythm factors on development of acute kidney injury after cardiac surgery using cardiopulmonary bypass: a retrospective cohort study
Xiaodong LI ; Jing WEN ; Xiao XU ; Xianjian LIAO ; Yuxi SONG ; Jiaxiang DUAN ; Kaizhi LU ; Bin YI ; Jiaolin NING
Chinese Journal of Anesthesiology 2024;44(9):1093-1096
Objective:To evaluate the effects of biorhythm factors on the occurrence of acute kidney injury (AKI) after cardiac surgery using cardiopulmonary bypass.Methods:This was a retrospective cohort study. Data from patients undergoing heart surgery involving cardiopulmonary bypass from June 2018 to December 2019 were collected and divided into 2 groups ( n=125 each) based on the time of anesthesia operation: morning rhythm group (group Ⅰ) and afternoon rhythm group (group Ⅱ). Anesthesia operation was performed from 8: 00 to 12: 00 in group Ⅰ. Anesthesia was performed from 14: 00 to 18: 00 in group Ⅱ. The occurrence of postoperative AKI and other postoperative complications (pulmonary infection, sepsis, cerebral infarction) was recorded. Results:Compared with group Ⅱ, the incidence of postoperative AKI was significantly increased, the relative risk was 3.2 (95% confidence interval 1.31-7.70), and no significant change was found in the incidence of pulmonary infection, sepsis and cerebral infarction in group Ⅰ ( P>0.05). Conclusions:Biorhythm factors affect the development of AKI after cardiac surgery using cardiopulmonary bypass, and performing surgeries in the afternoon rather than the morning helps reduce the risk of postoperative AKI.