The Study Of Protective Effects Of Edaravone Against Acute Paraquat Poisoning-induced Lung Injury In Rats

Objective：To explore the protective effects and mechanisms of edaravone in rats with acuteparaquat-induced lung injury.Method：144adult healthy SPF level Sprague-Dawley(SD) rats(female/male:1/1) wererandomly (random number) divided into the control group(group A), the edaravonegroup(group B), the PQ poisoning group(group C) and the edaravone treatmentgroup(group D), each group has36rats. The rat model of acute poisoning wasestablished by intra-gastric administration of40mg/kg PQ in rats of group C and D,the same volume of saline and edaravone was intragastricly administratedrespectively in rats of group A and B. After30minutes, edaravone(4mg/kg) wasinjected by peritoneal injection in group D, once a day, and equal volume normalsodium was injected by peritoneal injection in the other three grouops, once a day. Allthe rats were executed12、24、48、72h and14、28d after PQ poisoning respectivelyand samples were preserved. Were respectively to detect the12、24、48、72h four timepoints in four groups of serums SOD vitality and MDA content, and14、28d two tinepoints in four groups of serums TGF-β1and PⅢ P level; Macropathological and HEdyeing changes of lung tissue in each time point were observed.Results：(1) Changes of SOD vitality in serum: Compared with group A, SOD vitality inserum in group B was no significant difference in corresponding time point（sp>0.05）,but the SOD vitality in group C was decreased（p<0.05）; the SOD vitality in group Dwas lower than group A（12h，p<0.01；24、48、72h，p<0.05）, but higher than groupC（12h，p<0.05；24、48、72h，p<0.01）.(2) Changes of MDA content in serum: Compared with group A, MDA contentin serum in group C and group D was higher in corresponding time points（P0.01）,while there was no significant difference in group A and group B（p>0.05）;Compared with group C, MDA content in group D decreased significantly in serum in corresponding time points（12h，p<0.05；24、48、72h，p<0.01）.(3) Comparison of TGF-β1level in serum: There was no significant differencebetween group A and group B（p>0.05）; Compared with group A, TGF-β1level inserum in group C and group D increased significantly in corresponding time points（P0.01）; Compared with group C, there was singnificant decrease of TGF-β1levelin serum in group D（P0.01）.(4) Comparison of P ⅢP level in serum: Compared with group A，there was nosignificant difference in group B（p>0.05）, while P ⅢP level in group C and group Dwas increased singnificantly（P0.01）; the PⅢ P level in serum in group D was lowerthan group C （P0.01）.(5) Changes of histopathological changes of lung tissue: In group A and group B,the structures of the lung tissue were complete, there were not hyperemia orinfiltration of inflammatory cells in the alveolar space and alveolar septum. It wasshowed that alveolar wall thickening apparent, alveolar and interstitial pulmonaryedema, inflammatory cell infiltration and alveolar hemorrhage. With the extension ofthe poisoning time, there were varying degrees of fibroblast hyperplasia, collagendeposition in interstitial pulmonary and some alveolar structures had collapsed anddestroyed. The degree of hemorrhage, edema, inflammatory cells infiltration andpulmonary fibrosis in group D was significantly lessened compared with group C.Conclusions：(1) Serious oxidative stress was induced by PQ intoxication in experimental rats,over-reaction of lipid peroxidation involved in the cccurrence and development oflung injury, and a large number of cytokine TGF-1and P ⅢP play a vital role in theformation of pulmonary fibrosis in rats.(2) Edaravon can significantly improve the antioxidant capacity in rats inducedby PQ, inhibit lipid peroxidation, reduce oxygen free radical damage. At the sametime, edaravone also reduce pulmonary fibrosis in rats by inhibiting the expressionand release of cytokine TGF-1and the production of P ⅢP. Thus edaravone hasprotective roles in lung injury induced by acute PQ poinsoning.