| Objective To investigate the effect of the mechanical ventilation on brain tissue injury and brain function in rats by establishing acute lung injury model induced by mechanical ventilation in rats,and to explore the possible mechanismMethods There were 72 healthy adult male Wister rats,weighing about 180?220g,was provided by the comparative medical center of Yangzhou University,which were randomly divided into 4 groups:Group ?:spontaneous breathing after the completion of tracheal intubation.Group II:The tide volume was set at 40ml/kg,PEEP = 0mnHg.respiratory rate 40 times/min.respiration ratio(I:E)= 1:2.mechanical ventilation(VT)was set at 40ml/kg,PEEP=0mmHg,the respiratory rate was 40 times/min,and the tidal volume(VT)was set at 40ml/(I:E)= 1:2,the mechanical ventilation time was 6h;Group III:GABA 50mg/kg rats were given intraperitoneal administration,30min before large tidal volume mechanical ventilation,PEEP = 0mmHg.respiration ratio(I:E)= 1:2.tidal volume(VT)was set at 40 ml/kg,mechanical ventilation time was 6 h;Group ?:GABA receptor antagonist bicuculline 10?mol/kg rats were given intraperitoneal administration,30min beforelarge tidal volume mechanical ventilation,PEEP = OmmHg.respiration ratio(I:E)= 1:2,tidal volume(VT)was set at 40 ml/kg,mechanical ventilation time was 6 h;inhalation gas was air(oxygen concentration 21%).At the end of the mechanical ventilation.6 rats in each group were randomly selected for navigation experiments and space exploration experiments.The rest of the rats were killed by bloodletting rats,lung tissue,brain tissue specimens were taken for research.The wet/dry weight ratio(W/D ratio)and the permeability of Evans blue dye were measured.The pathological changes of lung tissue were observed and the score of lung injury was observed.TNF-??IL-1? and IL-18 in BALF were measured by enzyme-linked immunosorbent assay(ELISA).The apoptosis rate were measured by TUNEL staining.The expression of GABAAR protein in rat lung tissue was detected by SABC immunohistochemical staining and Western blot.The expression of GABAAR protein in rat brain was detected by Western blot.The expression of NSE,S-100? and TNF-? mRNA in brain tissue was detected by RT-PCR.Results Compared with group I,the W/D ratio,the infiltration rate of Evans blue dye.the inflammatory cytokine concentration in BALF,the apoptosis index of lung tissue,and the expression of NSE,S-100? and TNF-a mRNA in the brain tissue of rats in group ?,group ?and group IV were significantly increased(P<0.05).Compared with group ?,the expression of GABAAR protein in lung tissue and brain tissue of group @ and group ? were significantly increased(P<0.05).Compared with group I,the latencies of Morris water maze in Dayl and Day2 of group ?,group ? and group ? were significantly prolonged(P<0.05),and the percentage of swimming time in the platform quadrant was significantly decreased(P<0.05).Compared with group ?,the W/D ratio,the permeability of Evans blue dye,the inflammatory cytokine concentration in BALF were significantly higher than those in group ?(P<0.05).Compared with group II,the expression of NSE,S-100? and TNF-a mRNA in brain tissue of rats was significantly lower than that of group ?(P<0.05).Compared with group ?,the percentage of swimming time in group III rats was significantly higher than that in group II(P<0.05).Compared with group ?,rat lung tissue W/D ratio,Evans blue dye penetration rate,BALF inflammatory cytokine concentration,lung tissue cell apoptosis index,rat brain tissue NSE,S-100?,TNF-? rmRNA expression were significantly increased in group ?(P<0.05).Compared with group ?,the expression of GABAAR protein in lung tissue and brain tissue of group ? was significantly lower than that of group ?(P<0.05).Compared with group ?,Morris water maze was prolonged than that of group IV(P<0.05).Compared with group II,the percentage of swimming in the quadrant was decreased than that of group ?(P<0.05).Conclusion Large tidal volume of mechanical ventilation can not only lead to acute lung injury,but also lead to distant brain tissue damage.GABAAR plays an important role in lung-brain injury caused by mechanical ventilation.GABAAR can effectively reduce the pathological changes of lung tissue induced by mechanical ventilation,reduce alveolar and interstitial cell apoptosis,improve pulmonary edema and pulmonary vascular permeability changing and reduce the release of systemic inflammatory mediators;also can improve the brain tissue damage,reduce the brain tissue inflammatory mediators and improve the rat brain memory function.In summary,GABAAR is an endogenous protective mechanism that inhibits lung-brain injury caused by mechanical ventilation. |
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