Role And Significance Of Autophagy In Ventilator-Induced Lung Injury In Rat

Objective TO build an animal model of ventilator-induced lung injuy(VILI) in rats and evalute the effect of the high tidal volume on VILI in rat.Methods Thirty healthy SD rats were randomly divided into three groups(each 10 rats): control group(group A, no ventilation), conventional ventilation group(group B, VT=10 ml/Kg), lung injury group(group C, VT=40 ml/Kg). After anesthesia and tracheal intubation were installed,rats received ventilation with different volumes for 4 hours. Thus rats were killed by exsanguinations. The lung wet/dry weight was tested. The histopathological changes of lung tissue were observed by HE staining.Results After high tidal volume mechanical ventilation for 4 hours, no substantial changes of lung morphological were observed between group A and B. In the C group, the visible widened alveolar septum, the inflammatory cell infiltration and a large number of scattered bleeding points were observed in the lung tissues. Compared with the other two groups, the lung W/D ratio significantly increased in the C group(P < 0.05).Conclusion Ventilator-associated lung injury can be induced by the high tidal volume. Frome the testing results of the lung wet to dry weight and lung tissue pathological examination it can be proved that the animal model of ventilator-induced lung injury in rats was established successfully.Objective To investigate the role and significance of autophagy-related gene in a rat model of ventilator-induced lung injury(VILI).Methods Thirty healthy SD rats were randomly divided into three groups(each 10 rats): control group(group A, no ventilation), conventional ventilation group(group B, VT=10 ml/Kg), lung injury group(group C, VT=40 ml/Kg). After anesthesia and tracheal intubation were installed,rats received ventilation with different volumes for 4 hours. Thus rats were killed by exsanguinations. The lung MPO, SOD and MDA activity and total protein level and counts of white blood cells(WBC) in broneho-alveolar lavage fluid(BALF) were tested. Expression of TNF-? and IL-1? in BALF were detected by using ELISA method. Expression of HSP70 and NF-?B in the lung tissue were determined by using Western-blot.Results After injurious ventilation for 4 hours, the level of total protein level and counts of WBC and the expression of MPO and MDA were significantly increased(P<0.05),and the level of SOD was decreased(P<0.05). The expression of Beclin1, LC3 and NF-?B proteins were significantly increased(P<0.05).Moreover, this fuction could be inhibited by 3-methyladenine, a specific autophagy inhibitor.Conclusion Autophagy may play an important role in the process of inflammation response in the rat ventilator-induced lung injury, which may be related to the NF kappa B signaling pathway. This fuction can be inhibited by the specific autophagy inhibitor 3-MA, which indicated that autophagy may be a protective mechanism in the inflammation induced by VILI.