Protective Effect Of Exogenous Spermine On Lung Injury Caused By Paraquatand Its Mechanism

Objective:To explore the protective effect of exogenous spermine on the lung injury caused by paraquat and its mechanism,providing a new way of thinking and therapeutic method for the treatment of acute paraquat poisoning.Methods:120 male Sprague Dawley(SD)rats were randomly divided into 4 groups according to the random number table.Control group(C group),Paraquat group(PQ group),Paraquat+Spermine group(PQ+S group)and Spermine group(S group),30 rats in each group.Each group was divided into 3 subgroups,according to 3d,7d and 14 d time points,10 rats in each subgroup.Each Rats in the group PQ and PQ+S was given 1 ml0.9% Sodium Chloride Injection with 50 mg PQ/ kg weight,while each one in the C and S groups was given for 1ml 0.9% Sodium Chloride Injection,by gavage.Each Rats in the group PQ +S and S was given 2 ml spermine solution(0.1mmol/L)diluted by 0.9% sodium chloride injection at half an hour after the intragastric administration by peritoneal cavity injection.After that,the spermine solution of 0.9% Sodium Chloride Injection was injected into each animal's peritoneal cavity by 0.1mmol/L 2 ml every day until it was executed.Each Rats in the Group PQ and C was given 2 ml 0.9% sodium chloride injection into the peritoneal cavity daily until it was executed.Rats in each subgroup were executed respectively at each time point in 3 d,7 d and 14 days.The body weight before the execution and lung wet weight of rats were measured,and the lung coefficient of rats and the ratio in wet/dry of lung tissue(W/D)in each group were measured and compared to observe pulmonary edema.The lung in each group rats was excised for HE staining and Masson Staining to observe the degree of lung damage,while SOD,MDA contents and TGF-?1 expression levels in homogenate of lung tissue were tested.Results: PQ Group:on the day 3rd,manifested alveolar inflammation,on the day 7th,alveolar inflammation was reduced and a few pulmonary fibrosis was observed.On the day 14th,the degree of alveolitis continued to decrease,but pulmonary fibrosis was significant.The alveolar inflammation and pulmonary fibrosis of PQ+S Group were lower than PQ at each time point.No significant lung damage was observed in C group and S group.(1)On the day 3rd,7th and 14 th alveolitis classification scores of PQ Group and PQ+S Group were higher than C Group and S Group,alveolitis classification scores of PQ+S Group was much lower than PQ Group(P<0.05).On the day 3rd,7th and 14 thpulmonary fibrotic classification scores of PQ Group and PQ+S Group were higher than C Group and S Group,On the day 7th and 14 th pulmonary fibrotic scores of PQ+S Group was much lower than that PQ Group(P<0.05).while on the day 3rd pulmonary fibrotic classification scores of PQ+S Group was similar than PQ Group(P(29)0.05).(2)Each point in time,the lung coefficient of rats and the ratio in wet/dry of lung tissue(W/D)of PQ Group and PQ+S Group were higher than C Group and S Group,while PQ+S Group was much lower than that PQ Group(P<0.05).(3)Each point in time,TGF-?1 level in homogenate of lung tissue of rats in PQ Group and PQ+S Group were all higher than that in C Group and S Group,while PQ+S Group was much lower than PQ Group(P<0.05).(4)Each point in time,SOD level in homogenate of lung tissue of rats in PQ Group and PQ+S Group were all lower than that in C Group and S Group,while MDA level in PQ Group and PQ+S Group were all higher than that in C Group and S Group.SOD level in homogenate of lung tissue of rats in PQ+S Group were all higher than that in PQ Group,while MDA level in PQ+S Group were all lower than that in PQ Group(P<0.05).Conclusion: Exogenous spermine can effectively reduce the lung injury caused by paraquat,to reduce the mortality of paraquat poisoning rats,which is related to spermine inhibitting the high expression of MDA and TGF-beta 1 in the lung tissue of paraquat poisoning rats,and significantly increasing the level of SOD.