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Objective@#Through the study of angiotensinⅡ- type 2 receptor agonist (AT2R) after pretreatment of mechanical ventilation lung injury (VILI) in rats model, to clarify the role of angiotensin Ⅱ - type 2 receptor agonist (C21) in alleviating VILI inflammation and the damage of immune function and its possible mechanism.@*Methods@#In this experiment, the acute lung injury model was established by mechanical spring-volume ventilation in SD rats, and C21 pretreatment was performed to observe the pathological condition of lung tissue in rats with different ventilation duration, and to detect the inflammatory changes of BALF lavage fluid. Flow cytometry was used to detect the CD68+/iNOS+ labeled M1 type AMφ and the CD68+/Arg-1+ labeled M2 type AMφ in alveolar lavage fluid.@*Results@#The mechanical VILI rat model was successfully established. The pathological injury score of the mechanical ventilation 4 h model, the wet/dry weight of lung tissue, the number of cells and protein in BALF lavage fluid were increased significantly, the levels of TNF-α and IL - 1 were increased significantly, the levels of IL-4 and IL-10 were decreased significantly, and the level of inflammatory reaction decreased with the increase of ventilation time. The M1/M2 ratio in the 4 h ventilation model group was the highest, which was significantly different from the control group (P<0.05). Compared to the model group, the C21 pretreatment significantly reduced the levels of proinflammatory factors TNF-αand IL-1, and increased the levels of anti-inflammatory factors IL-4 and IL-10 in BALF (P<0.01). After the intervention of AT2R agonist at 4 h, 6 h and 8 h, the M1/M2 ratio of the model was lower than that of the model without AT2R agonist at 4 h, 6 h and 8 h.@*Conclusion@#Mechanical ventilation for 4 h in SD rats can establish a mechanical ventilation lung injury model. AT2R agonist C21 can promote the polarization of macrophages to m2-type, and C21 pretreatment may alleviate VILI inflammation and immune damage by altering the polarization of macrophages.
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Objective Through the study of angiotensin Ⅱ-type 2 receptor agonist(AT2R)after pretreatment of mechanical ventilation lung injury(VILI)in rats model,to clarify the role of angiotensin Ⅱ-type 2 receptor agonist(C21)in alleviating VILI inflammation and the damage of immune function and its possible mechanism.Methods In this experiment,the acute lung injury model was established by mechanical spring-volume ventilation in SD rats,and C21 pretreatment was performed to observe the pathological condition of lung tissue in rats with different ventilation duration,and to detect the inflammatory changes of BALF lavage fluid.Flow cytometry was used to detect the CD68+/INOS+labeled M 1 type Amφ and the CD68+/Arg-1+labeled M2 type Amφ in alveolar lavage fluid.Results The mechanical VILI rat model was successfully established.The pathological injury score of the mechanical ventilation 4 h model,the wet/dry weight of lung tissue,the number of cells and protein in BALF lavage fluid were increased significantly,the levels of TNF-α and IL-1 were increased significantly,the levels of IL-4 and IL-10 were decreased significantly,and the level of inflammatory reaction decreased with the increase of ventilation time.The M1/M2 ratio in the 4 h ventilation model group was the highest,which was significantly different from the control group(P＜0.05).Compared to the model group,the C21 pretreatment significantly reduced the levels of proinflammatory factors TNF-α and IL-1,and increased the levels of anti-inflammatory factors IL-4 and IL-10 in BALF(P＜O.O1).After the intervention of AT2R agonist at 4 h,6 h and 8 h,the M1/M2 ratio of the model was lower than that of the model without AT2R agonist at 4 h,6 h and 8 h.Conclusion Mechanical ventilation for 4 h in SD rats can establish a mechanical ventilation lung injury model.AT2R agonist C21 can promote the polarization of macrophages to m2-type,and C21 pretreatment may alleviate VILI inflammation and immune damage by altering the polarization of macrophages.
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Objective To investigate the protective effects of Platycodon grandiflorum total saponins (PGTS) on acute lung injury (ALI) in rats and the related mechanisms.Methods Total of 60 SD rats were randomly (random number) divided into control group,model group,low-,middle-and high-dose PGTS group,and dexamethasone group,10 rats in each group.The latter 4 groups and dexamethasone group were injected with 50,100,200 mg/kg PGTS and 5 mg/kg dexamethasone,respectively.After 1 h,the latter 5 groups were intraperitoneally injected with mg/kg LPS to establish the ALI model.The clinical symptoms of the rats were observed.After 12 h,the arterial PaO2 and PaCO2,serum TNF-α and IL-10 level,lung wet/dry weight ratio (W/D),lung tissue SOD,GSH-Px and MDA level and NF-κB protein expression were determined.Results Rats in model group manifested noticeable symptoms of acute lung injury (ALI) and lung tissue lesions.In treatment group with appropriate PGTS dose,ALI symptoms and lung lesions were significantly alleviated,arterial PaO2 was markedly increased (P ＜ 0.05),PaCO2 was decreased obviously (P ＜ 0.05),serum TNF-α level was prominently decreased (P ＜ 0.05),IL-10 level was strikingly decreased (P ＜ 0.05),lung W/D ratio was significantly decreased (P ＜0.05),lung tissue SOD and GSH-Px level were distincdy increased (P ＜0.05),MDA was clearly decreased (P ＜ 0.05),and NF-κB protein expression was plainly decreased (P ＜ 0.05),compared with model group.Conclusions PGTS has undoubted protective effects on acute lung injury induced by LPS in rats.The mechanism may be associated with its role of anti-inflammation,anti-lipid peroxidation and down regulation of NF-κB protein level in lung tissue.
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Aim To investigate the changes of phosphodiesterase4(PDE4,type 4 cAMP-specific PDE) activity,TNF-? and neutrophil recruitment in experimental rat lung injury(ALI).Methods ALI in the rat was induced by lipopolysacdharide(LPS).PDE4 activity was measured with HPLC,and the level of TNF-? was detected with ELISA,neutrophil infiltration in bronchoalveolar lavage fluid(BALF) and lung tissues was detected by cell count and morphological analysis.Result Lung tissue PDE4 activity significantly increased as early as 1 h,peaked 6 h,and then markedly lowered at 24 h after intratracheal administration of LPS,while there was a same time-course change of total white cell and neutrophil in the BALF(r=0.83,P