Protective Effect Of Qingyi Ⅱ On Acute Lung Injury Induced By Sepsis

Objective: Through estabilishing the rat’s mdoel of acute lung injury induced by sepsis,observing the indicator of oxidative stress and related pathway and the pathological changes of the lung,to explore the protective effect of Qingyi II on acute lung injury induced by sepsis.Methods: 108 healthy adult male Sprague-Dawley rats were randomly divided into 3groups including sham group,model group and treatment group.Each group was randomly divided into 3 subgroups,which were observation group,24 h sampling group,and 72 hour sampling group.Sham group only open the abdomen and find the cecum,then put it back and seam the abdominal cavity.Model group and treatment group were used to construct the model of the acute lung injury induced by sepsis by the method of cecal ligation and puncture.Each group were immediately given intraperitoneal injection of 37 °C normal saline 3 ml/100 g to supply the intraoperative fluid loss ofter operation.Treatment group was given 1 ml/100 g of Qingyi II per 12 hours by means of intragastric administation 1hour after operation,and the sham group and model group were given the same dose of normal saline at the same time by means of intragastric administration.The rats in each group were anesthetized at 24 hours and 72 hours after operation then to detect SOD,MDA,GSH and CAT index of blood collected from the abdominal aorta.The tissues of lung and brain were quickly weighed and determined the lung-brain ratio.The left lower lobe was embedded in paraffin for HE staining and pathological scoring of lung injury;Nrf2,HO-1,NQO1 were determined by immunohistochemistry stain.The right lower lobe were collected and then stored in a-80 ℃ refrigerator for making frozen sections(thickness 20 μm),then to detect the ROS index.The survival of each group of rats was observed every 12 hours,and the observation was terminated when all the rats in the observation group died.Results: The survival time of the model group was 45.59±5.62 hours,and the cumulative survival rate was 0.0%.The survival time of the treatment group was 62.78±5.74 hours,and the cumulative survival rate was 32.1%.The survival time between the two groups was different(P<0.05).At 24 h,the symptoms of the model group and the treatment group were similar,all of which showed mental wilting and shortness of breath.Both of them were less sensitive to external stimuli and progressively worsened symptoms over time.The above symptoms of rats in treatment group were obviously improved at 72 h after the treatment of Qingyi II compared with that at 24 h.HE staining of lung tissue pathological section of rats in B group at 24 h showed pulmonary congestion and edema,a large number of inflammatory cell infiltration,and the changes which were more obvious over time;lung tissue edema,infiltration of inflammatory cells were decreased in group C at 72 h.Compared with group A,the pathological scores of lung injury in group B and C were significantly increased at 24 h and 72h(P<0.05).Compared with group B,the pathological score of lung injury in group C was not statistically significant.(P > 0.05),but the difference was statistically significant at 72h(P<0.05).Compared with group A,the ratio of lung-brain in group B and group C was significantly increased at 24 h and 72h(P<0.05),but there was no statistical difference between group B and group C at 24h(P<0.05).The proportion of lung-brain in group C was lower than that in group B at 72 hours(P<0.05).Compared with group A,SOD activity,GSH content and CAT activity was decreased in group B and group C at 24 h and 72h(P<0.05),and MDA content and ROS expression in lung tissue obvious increased(P<0.05).There was no statistical difference between group B and group C at 24h(P>0.05).Compared with group B,SOD activity,CAT activity and GSH content in group C increased significantly(P>0.05),and MDA content and ROS expression in lung tissue obviously decreased(P<0.05).Nrf2,HO-1 and NQO1 proteins were widely expressed in bronchial epithelium,alveolar epithelium and inflammatory cells.Compared with group A,the expression of Nrf2,HO-1 and NQO1 protein in group B and group C were significantly increased at 24 h and 72h(P<0.05).There was no significant difference between group B and group C at 24h(P>0.05);The expression of Nrf2,HO-1and NQO1 protein in group C at 72 h was higher than that in group B(P<0.05).Conclusion: Qingyi II can effectively improve the survival time of acute lung injury caused by sepsis.The protective effect may be related to the activation of Nrf2-ARE pathway.