The Research Of Protective Effect Of Mast Cell Stabilizer On Lung Injury Induced By Paraquat In Mice

Objective：To establish the mouse model of paraquat-induced lung injury,investigate the protective effect of mast cell stabilizer on lung injury induced byparaquat in mice.Methods：Thirty-six female Kunming mice were randomly divided into controlgroup,paraquat group,captopril group and sodium cromolyn group. There were18mice in paraquat group,and6mice in the rest three groups.Each mouse in controlgroup was injected intraperitoneally1ml saline,after0.5h and then every12h eachmouse was injected intraperitoneally1ml saline till being sacrificed at72h.Eachmouse in PQ group was injected intraperitoneally PQ(by30mg/Kg body weightstandard),after0.5h and then every12h each mouse was injected intraperitoneally1ml saline till being sacrificed，6mice were sacrificed at8h、24h and72h.Eachmouse in captopril group was injected intraperitoneally PQ(by30mg/Kg bodyweight standard),after0.5h and then every12h each mouse was injectedintraperitoneally captopril(by10mg/Kg body weight standard) till being sacrificed at72h.Each mouse in cromolyn sodium group was injected intraperitoneally PQ(by30mg/Kg body weight standard),after0.5h and then every12h each mouse wasinjected intraperitoneally cromolyn sodium(by25mg/Kg body weight standard) tillbeing sacrificed at72h.After administration,mice were observed of mental state, hairchanges,behavioral changes and so on.We observed the lungs and put them into10%neutral. The lungs in PQ group at8h and24h were only for HE staining；andthe lungs in each group at72h were for HE staining,Masson staining, COX-2、TGF-β1and CD68immunohistochemistry.Results：(1) Mice in PQ group appeared poisoning symptoms after PQpoisoning,and the symptoms gradually increased with time.The poisoning symptomsof mice in captopril group and cromolyn sodium group were reduced compared withPQ group,but there was no significant difference between captopril group andcromolyn sodium group.(2) The lungs of mice in control group were pink with normal form and smooth surface.The lung volume of mice in PQ group,captoprilgroup and cromolyn sodium group was increased significantly,most of the lungsurface was dark red, and the lung was medium texture with congestion and exudatein section,PQ group was the worst.(3) The HE staining showed: the lung tissue incontrol group was structural integrity;the lung tissue in PQ group appeared seriousinflammatory reaction,and lung injury score was increased significantly by time(P＜0.05).The lung tissue in captopril group and cromolyn sodium group alsoappeared inflammatory reaction,but better than PQ group.Compared with the controlgroup,lung injury score of the rest three groups were observably higher(P＜0.05).Lung injury score of captopril group and cromolyn sodium group were lowerthan PQ group,and cromolyn sodium group were lower than captopril group.(4)TheMasson staining showed:the blue staining density of lung in PQ group,captoprilgroup and cromolyn sodium group were remarkably increased compared withcontrol group(P＜0.01),captopril group and cromolyn sodium group were lower thanPQ group(P＜0.05),captopril group was higher than cromolyn sodium group(P＜0.05).(5)The CD68+macrophages in lungs in PQ group,captopril group andcromolyn sodium group were remarkably higher than control group(P＜0.0001),captopril group and cromolyn sodium group were lower than PQ group(P＜0.05),captopril group was higher than cromolyn sodium group(P＜0.05).(6)Theexpression of COX-2in lung in PQ group,captopril group and cromolyn sodiumgroup were obviously higher than control group(P＜0.05), captopril group andcromolyn sodium group were lower than PQ group(P＜0.05),captopril group washigher than cromolyn sodium group(P＜0.05).(6)The expression of TGF-β1in lungin PQ group,captopril group and cromolyn sodium group were signally higher thancontrol group(P＜0.01), captopril group and cromolyn sodium group were lowerthan PQ group(P＜0.05),captopril group was higher than cromolyn sodium group(P＜0.05).Conclusion：(1) Intraperitoneal injection of PQ by30mg/kg weight cansuccessfully establish Kunming mouse model of paraquat-induced lung injury；(2)Cromolyn sodium can decrease inflammatory cell infiltration in lung tissue of mice after paraquat poisoning；(3) Cromolyn sodium can decrease pulmonary inflammatoryedema and fibrosis in lung tissue of mice after paraquat poisoning;(4) Mast cellsstabilizers play a protective role on lung injury induced by paraquat in mice.